Insecticidal compounds

ABSTRACT

A compound of formula (I), wherein A 1 , A 2 , A 3 , A 4 , G 1 , L, R 1 , R 2 , R 3 , R 4 , Y 1 , Y 2  and Y 3  are as defined in claim  1 ; or a salt or N-oxide thereof. Furthermore, the present invention relates to processes and intermediates for preparing compounds of formula (I), to insecticidal, acaricidal, molluscicidal and nematicidal compositions comprising them and to methods of using them to combat and control insect, acarine, mollusc and nematode pests.

This application is a 371 of International Application No.PCT/EP2008/010701 filed Dec. 16, 2008, which claims priority to GB0725219.0 filed Dec. 24, 2007, and GB 0813849.7 filed Jul. 29, 2008, thecontents of which are incorporated herein by reference.

The present invention relates to certain benzamide isoxazolines, toprocesses and intermediates for preparing them, to insecticidal,acaricidal, molluscicidal and nematicidal compositions comprising themand to methods of using them to combat and control insect, acarine,mollusc and nematode pests.

Certain isoxazoline derivatives with insecticidal properties aredisclosed, for example, in EP 1,731,512, US 2007/066617, JP 2007/008914,JP 2007/016017, EP 1,932,836, JP 2007/106756, WO 07/070606, EP 1,975,149and WO 07/075459.

It has now surprisingly been found that certain benzamide isoxazolineshave insecticidal properties.

The present invention therefore provides a compound of formula (I)

wherein

-   A¹, A², A³ and A⁴ are independently of one another C—H, C—R⁵, or    nitrogen;-   G¹ is oxygen or sulfur;-   L is a single bond, C₁-C₈alkyl, C₁-C₈haloalkyl, C₂-C₈alkenyl,    C₂-C₈haloalkenyl, C₂-C₈alkynyl, or C₂-C₈haloalkynyl;-   R¹ is hydrogen, C₁-C₈alkyl, C₁-C₈alkylcarbonyl-, or    C₁-C₈alkoxycarbonyl-;-   R² is hydrogen, or C₁-C₈alkyl;-   R³ is C₁-C₈haloalkyl;-   R⁴ is aryl or aryl substituted by one to three R⁶, or heterocyclyl    or heterocyclyl substituted by one to three R⁶;-   Y¹, Y² and Y³ are independently of another CR⁷R⁸, C═O, C═N—OR⁹,    N—R⁹, S, SO, SO₂, S═N—R⁹, or SO═N—R⁹, provided that at least one of    Y¹, Y² or Y³ is not CR⁷R⁸;-   each R⁵ is independently halogen, cyano, nitro, C₁-C₈alkyl,    C₁-C₈haloalkyl, C₂-C₈alkenyl, C₂-C₈haloalkenyl, C₂-C₈alkynyl,    C₂-C₈haloalkynyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy,    C₁-C₈alkoxycarbonyl-, aryl or aryl optionally substituted by one to    three R¹⁰, or heteroaryl or heteroaryl optionally substituted by one    to three R¹⁰, or where two R⁵ are adjacent, the two R⁵ may together    with the carbon atoms to which the two R⁵ are bonded form a    5-membered ring, wherein the 5-membered ring is —OCH═N—, —SCH═N—,    —OCR¹⁰═N—, or —SCR¹⁰═N—; each R⁶ is independently halogen, cyano,    nitro, C₁-C₈alkyl, C₁-C₈haloalkyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy, or    C₁-C₈alkoxycarbonyl-;-   each R⁷ and R⁸ is independently hydrogen, halogen, C₁-C₈alkyl, or    C₁-C₈haloalkyl;-   each R⁹ is independently hydrogen, cyano, nitro, C₁-C₈alkyl,    C₁-C₈haloalkyl, C₁-C₈alkylcarbonyl-, C₁-C₈haloalkylcarbonyl-,    C₁-C₈alkoxycarbonyl-, C₁-C₈haloalkoxycarbonyl-, C₁-C₈alkylsulfonyl-,    C₁-C₈haloalkylsulfonyl-, aryl-C₁-C₄alkyl- or aryl-C₁-C₄alkyl-    wherein the aryl moiety is substituted by one to three R¹¹, or    heteroaryl-C₁-C₄alkyl- or heteroaryl-C₁-C₄alkyl- wherein the    heteroaryl moiety is substituted by one to three R¹¹;-   each R¹⁰ is independently halogen, cyano, nitro, C₁-C₈alkyl,    C₁-C₈haloalkyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy, or    C₁-C₈alkoxycarbonyl-; and-   each R¹¹ is independently halogen, cyano, nitro, C₁-C₈alkyl,    C₁-C₈haloalkyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy, or    C₁-C₈alkoxycarbonyl-; or a salt or N-oxide thereof.

The compounds of formula (I) may exist in different geometric or opticalisomers or tautomeric forms. This invention covers all such isomers andtautomers and mixtures thereof in all proportions as well as isotopicforms such as deuterated compounds.

The compounds of the invention may contain one or more asymmetric carbonatoms, for example, in the —CR³R⁴— group or at the LR²Y¹Y³ carbon andmay exist as enantiomers (or as pairs of diastereoisomers) or asmixtures of such. Further, where any Y group is SO, the compounds of theinvention are sulfoxides, which can also exist in two enantiomericforms.

Each alkyl moiety either alone or as part of a larger group (such asalkoxy, alkylcarbonyl, or alkoxycarbonyl) is a straight or branchedchain and is, for example, methyl, ethyl, n-propyl, prop-2-yl, n-butyl,but-2-yl, 2-methyl-prop-1-yl or 2-methyl-prop-2-yl. The alkyl groups arepreferably C₁ to C₆ alkyl groups, more preferably C₁-C₄ and mostpreferably C₁-C₃ alkyl groups.

Alkenyl moieties can be in the form of straight or branched chains, andthe alkenyl moieties, where appropriate, can be of either the (E)- or(Z)-configuration. Examples are vinyl and allyl. The alkenyl groups arepreferably C₂-C₆, more preferably C₂-C₄ and most preferably C₂-C₃alkenyl groups.

Alkynyl moieties can be in the form of straight or branched chains.Examples are ethynyl and propargyl. The alkynyl groups are preferablyC₂-C₆, more preferably C₂-C₄ and most preferably C₂-C₃ alkynyl groups.

Halogen is fluorine, chlorine, bromine or iodine.

Haloalkyl groups (either alone or as part of a larger group, such ashaloalkoxy) are alkyl groups which are substituted by one or more of thesame or different halogen atoms and are, for example, trifluoromethyl,chlorodifluoromethyl, 2,2,2-trifluoro-ethyl or 2,2-difluoro-ethyl.

Haloalkenyl groups are alkenyl groups, respectively, which aresubstituted with one or more of the same or different halogen atoms andare, for example, 2,2-difluorovinyl or 1,2-dichloro-2-fluoro-vinyl.

Haloalkynyl groups are alkynyl groups, respectively, which aresubstituted with one or more of the same or different halogen atoms andare, for example, 1-chloro-prop-2-ynyl.

In the context of the present specification the term “aryl” refers to aring system which may be mono-, bi- or tricyclic. Examples of such ringsinclude phenyl, naphthalenyl, anthracenyl, indenyl or phenanthrenyl. Apreferred aryl group is phenyl.

The term “heteroaryl” refers to an aromatic ring system containing atleast one heteroatom and consisting either of a single ring or of two ormore fused rings. Preferably, single rings will contain up to threeheteroatoms and bicyclic systems up to four heteroatoms which willpreferably be chosen from nitrogen, oxygen and sulfur. Examples ofmonocyclic groups include pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl,pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, furanyl,thiophenyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl,and thiadiazolyl. Examples of bicyclic groups include quinolinyl,cinnolinyl, quinoxalinyl, benzimidazolyl, benzothiophenyl, andbenzothiadiazolyl. Monocyclic heteroaryl groups are preferred, pyridylbeing most preferred.

The term “heterocyclyl” is defined to include heteroaryl and in additiontheir unsaturated or partially unsaturated analogues.

Preferred values of A¹, A², A³, A⁴, G¹, L, R¹, R², R³, R⁴, Y¹, Y², Y³,R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, and R¹¹, are, in any combination, as set outbelow.

Preferably no more than two of A¹, A², A³ and A⁴ are nitrogen.

Preferably A¹ is C—H or C—R⁵, most preferably A¹ is C—R⁵.

Preferably A² is C—H or C—R⁵, most preferably A² is C—H.

Preferably A³ is C—H or C—R⁵, most preferably A³ is C—H.

Preferably A⁴ is C—H or C—R⁵, most preferably A⁴ is C—H.

Preferably G¹ is oxygen.

Preferably L is a single bond, C₁-C₈alkyl, or C₁-C₈haloalkyl, morepreferably a single bond, or C₁-C₈alkyl, even more preferably a singlebond or C₁-C₂alkyl, yet even more preferably a single bond or methyl,most preferably a single bond.

Preferably R¹ is hydrogen, methyl, ethyl, methylcarbonyl-, ormethoxycarbonyl-, more preferably hydrogen, methyl or ethyl, even morepreferably hydrogen or methyl, most preferably hydrogen.

Preferably R² is hydrogen or methyl, most preferably hydrogen.

Preferably R³ is chlorodifluoromethyl or trifluoromethyl, mostpreferably trifluoromethyl.

In one group of preferred compounds R⁴ is aryl or aryl substituted byone to three R⁶, more preferably R⁴ is phenyl or phenyl substituted byone to three R⁶, even more preferably R⁴ is phenyl substituted by one tothree R⁶, more preferably R⁴ is 3,5-bis-(trifluoromethyl)-phenyl,3,5-dibromo-phenyl, 3,5-dichloro-phenyl, 3,4-dichloro-phenyl,3-trifluoromethyl-phenyl, or 3,4,5-trichloro-phenyl, yet even morepreferably R⁴ is 3,5-dibromo-phenyl, 3,5-dichloro-phenyl,3,4-dichloro-phenyl, or 3,4,5-trichloro-phenyl, most preferably R⁴ is3,5-dichloro-phenyl.

In another preferred group of compounds R⁴ is heterocyclyl orheterocyclyl substituted by one to three R⁶, more preferably R⁴ isheteroaryl or heteroaryl substituted by one to three R⁶, even morepreferably R⁴ is pyridyl or pyridyl substituted by one to three R⁶, mostpreferably R⁴ is pyridyl substituted by one to three R⁶.

Preferably Y¹, Y² and Y³ are independently of another CR⁷R⁸, C═O,C═N—OR⁹, N—R⁹, S, SO, SO₂, S═N—R⁹, or SO═N—R⁹, provided that one of Y¹,Y² or Y³ is not CR⁷R⁸, more preferably Y¹, Y² and Y³ are independentlyof another CR⁷R⁸, N—R⁹, S, SO, SO₂, S═N—R⁹, or SO═N—R⁹, provided thatone of Y¹, Y² or Y³ is not CR⁷R⁸, even more preferably Y¹, Y² and Y³ areindependently of another CR⁷R⁸, S, SO, or SO₂, provided that one of Y¹,Y² or Y³ is not CR⁷R⁸, most preferably Y² is S, SO, or SO₂, and Y¹ andY³ are independently of another CR⁷R⁸.

In one embodiment Y¹ is C═O, C═N—OR⁹, N—R⁹, S, SO, SO₂, S═N—R⁹, orSO═N—R⁹, and Y² and Y³ are independently of another CR⁷R⁸.

In one embodiment Y² is C═O, C═N—OR⁹, N—R⁹, S, SO, SO₂, S═N—R⁹, orSO═N—R⁹, and Y¹ and Y³ are independently of another CR⁷R⁸.

Preferably each R⁵ is independently halogen, cyano, nitro, C₁-C₈alkyl,C₁-C₈haloalkyl, C₂-C₈alkenyl, C₂-C₈haloalkenyl, C₂-C₈alkynyl,C₂-C₈haloalkynyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy, or C₁-C₈alkoxycarbonyl-,more preferably halogen, cyano, nitro, C₁-C₈alkyl, C₁-C₈haloalkyl,C₁-C₈alkoxy, C₁-C₈haloalkoxy, or C₁-C₈alkoxycarbonyl-, even morepreferably bromo, chloro, fluoro, cyano, nitro, methyl, ethyl,trifluoromethyl, methoxy, difluoromethoxy, trifluoromethoxy, ormethoxycarbonyl-, yet even more preferably bromo, chloro, fluoro, nitro,or methyl, most preferably chloro, fluoro, or methyl.

Preferably each R⁶ is independently bromo, chloro, fluoro, cyano, nitro,methyl, ethyl, trifluoromethyl, methoxy, difluoromethoxy,trifluoromethoxy, or methoxycarbonyl-, more preferably chloro, fluoro,cyano, nitro, methyl, ethyl, trifluoromethyl, methoxy, ortrifluoromethoxy, most preferably bromo, chloro, or fluoro.

Preferably each R⁷ and R⁸ is independently hydrogen or methyl, mostpreferably hydrogen.

Preferably each R⁹ is independently hydrogen, cyano, methyl,trifluoromethyl, methylcarbonyl-, trifluoromethylcarbonyl-,methoxycarbonyl-, trifluoromethoxycarbonyl-, methylsulfonyl-,trifluoromethylsulfonyl-, or benzyl or benzyl wherein the phenyl moietyis substituted by one to three R¹⁰, most preferably hydrogen, methyl,trifluoromethyl, or benzyl or benzyl wherein the phenyl moiety issubstituted by one to three R¹⁰.

Preferably each R¹⁰ is independently bromo, chloro, fluoro, cyano,nitro, methyl, ethyl, trifluoromethyl, methoxy, difluoromethoxy,trifluoromethoxy, or methoxycarbonyl-, more preferably chloro, fluoro,cyano, nitro, methyl, ethyl, trifluoromethyl, methoxy, ortrifluoromethoxy, most preferably bromo, chloro, or fluoro.

Preferably each R¹¹ is independently bromo, chloro, fluoro, cyano,nitro, methyl, ethyl, trifluoromethyl, methoxy, difluoromethoxy,trifluoromethoxy, or methoxycarbonyl-, more preferably chloro, fluoro,cyano, nitro, methyl, ethyl, trifluoromethyl, methoxy, ortrifluoromethoxy, most preferably bromo, chloro, or fluoro.

A preferred embodiment are compounds of formula (Ia) wherein A¹ is C—R⁵,A², A³, and A⁴ are C—H, R⁴ is 3,5-dichloro-phenyl, L is a bond, and G¹,R¹, R², R³, Y¹, Y², and Y³ are as defined for a compound of formula (I);or a salt or N-oxide thereof.

A preferred embodiment are compounds of formula (Ia.A) wherein A¹ isC—Br, A², A³, and A⁴ are C—H, R⁴ is 3,5-dichloro-phenyl, L is a bond,and G¹, R¹, R², R³, Y¹, Y², and Y³ are as defined for a compound offormula (I); or a salt or N-oxide thereof.

A preferred embodiment are compounds of formula (Ia.B) wherein A¹ isC—CN, A², A³, and A⁴ are C—H, R⁴ is 3,5-dichloro-phenyl, L is a bond,and G¹, R¹, R², R³, Y¹, Y², and Y³ are as defined for a compound offormula (I); or a salt or N-oxide thereof.

A preferred embodiment are compounds of formula (Ia.C) wherein A¹ isC-Me, A², A³, and A⁴ are C—H, R⁴ is 3,5-dichloro-phenyl, L is a bond,and G¹, R¹, R², R³, Y¹, Y², and Y³ are as defined for a compound offormula (I); or a salt or N-oxide thereof.

A preferred embodiment are compounds of formula (Ia.D) wherein A¹ isC—CF₃, A², A³, and A⁴ are C—H, R⁴ is 3,5-dichloro-phenyl, L is a bond,and G¹, R¹, R², R³, Y¹, Y², and Y³ are as defined for a compound offormula (I); or a salt or N-oxide thereof.

A preferred embodiment are compounds of formula (Ib) wherein A¹ is C—R⁵,A², A³, and A⁴ are C—H, R⁴ is 3,5-dichloro-phenyl, L is CH₂, and G¹, R¹,R², R³, Y¹, Y², and Y³ are as defined for a compound of formula (I); ora salt or N-oxide thereof.

Certain intermediates are novel and as such form a further aspect of theinvention. One group of novel intermediates are compounds of formula(XI)

wherein A¹, A², A³, A⁴, G¹, L, R¹, R², and Y³ are as defined for acompound of formula (I); or a salt or N-oxide thereof. The preferencesfor A¹, A², A³, A⁴, G¹, L, R¹, R², Y¹, Y² and Y³ are the same as thepreferences set out for the corresponding substituents of a compound offormula (I).

Another group of novel intermediates are compounds of formula (XI′)

wherein A¹, A², A³, A⁴, G¹, L, R¹, R², Y¹, Y² and Y³ and Y³ are asdefined for a compound of formula (I); or a salt or N-oxide thereof. Thepreferences for A¹, A², A³, A⁴, G¹, L, R¹, R², Y¹, Y² and Y³ are thesame as the preferences set out for the corresponding substituents of acompound of formula (I).

Another group of novel intermediates are compounds of formula (XII)

wherein A¹, A², A³, A⁴, G¹, L, R¹, R², Y¹, Y² and Y³ are as defined fora compound of formula (I); or a salt or N-oxide thereof. The preferencesfor A¹, A², A³, A⁴, G¹, L, R¹, R², Y¹, Y² and Y³ are the same as thepreferences set out for the corresponding substituents of a compound offormula (I).

Another group of novel intermediates are compounds of formula (XIII)

wherein A¹, A², A³, A⁴, G¹, L, R¹, R², Y¹, Y² and Y³ are as defineformula (I) and X^(B) is a leaving group, for example a halogen, such asbromo; or a salt or N-oxide thereof. The preferences for A¹, A², A³, A⁴,G¹, L, R¹, R², Y¹, Y² and Y³ are the same as the preferences set out forthe corresponding substituents of a compound of formula (I).

Another group of novel intermediates are compounds of formula (XIII)wherein A¹, A², A³, A⁴, G¹, L, R¹, R², Y¹, Y² and Y³ are as defined fora compound of formula (I) and X^(B) is a leaving group, for example ahalogen, such as bromo; or a salt or N-oxide thereof, provided that thecompound is not3-chloro-4-fluoro-N-{1-[1-(4-methoxy-2,3-dimethyl-phenyl)ethyl]-3-azetidinyl}-benzamide(CAS RN 1005461-02-8),3-chloro-4-fluoro-N-[{1-[1-(4-methoxy-2,3-dimethylphenyl)ethyl]-3-azetidinyl}methyl]-benzamide(CAS RN 1005471-81-7),3-chloro-4-fluoro-N-[{1-[1-(4-methoxy-2,3-dimethylphenyl)propyl]-3-azetidinyl}methyl]-benzamide(CAS RN 1005472-44-5), or3-chloro-4-fluoro-N-[{1-[1-(4-methoxy-2,3-dimethylphenyl)methyl]-3-azetidinyl}methyl]-benzamide(CAS RN 1005472-60-5). The preferences for A¹, A², A³, A⁴, G¹, L, R¹,R², Y¹, Y² and Y³ are the same as the preferences set out for thecorresponding substituents of a compound of formula (I).

Another group of novel intermediates are compounds of formula (XIII)wherein A¹, A², A³, A⁴, G¹, L, R¹, R², Y¹, Y² and Y³ are as defined fora compound of formula (I) and X^(B) is a leaving group, for example ahalogen, such as bromo; or a salt or N-oxide thereof, provided that ifone of Y¹, Y² and Y³ is N—R⁹, the remaining Y¹, Y² and Y³ cannot a) bothbe CR⁷R⁸, or b) be CR⁷R⁸ and C═O, respectively. The preferences for A¹,A², A³, A⁴, G¹, L, R¹, R², Y¹, Y² and Y³ are the same as the preferencesset out for the corresponding substituents of a compound of formula (I).

Another group of novel intermediates are compounds of formula (XIV)

wherein A¹, A², A³, A⁴, G¹, L, R¹, R², Y¹, Y² and Y³ are as defined fora compound of formula (I); or a salt or N-oxide thereof. The preferencesfor A¹, A², A³, A⁴, G¹, L, R¹, R², Y¹, Y² and Y³ are the same as thepreferences set out for the corresponding substituents of a compound offormula (I).

Another group of novel intermediates are compounds of formula (XV)

wherein A¹, A², A³, A⁴, G¹, L, R¹, R², Y¹, Y², and Y³ are as defined fora compound of formula (I); or a salt or N-oxide thereof. The preferencesfor A¹, A², A³, A⁴, G¹, L, R¹, R², Y¹, Y² and Y³ are the same as thepreferences set out for the corresponding substituents of a compound offormula (I).

Another group of novel intermediates are compounds of formula (XVIII)

wherein A¹, A², A³, A⁴, G¹, L, R¹, R², Y¹, Y² and Y³ are as defined fora compound of formula (I); or a salt or N-oxide thereof. The preferencesfor A¹, A², A³, A⁴, L, R¹, R², Y¹, Y² and Y³ are the same as thepreferences set out for the corresponding substituents of a compound offormula (I).

Another group of novel intermediates are compounds of formula (XIX)

wherein A¹, A², A³, A⁴, L, R¹, R², R³, R⁴, Y¹, Y² and Y³ are as definedfor a compound of formula (I); or a salt or N-oxide thereof. Thepreferences for A¹, A², A³, A⁴, G¹, L, R¹, R², R³, R⁴, Y¹, Y² and Y³ arethe same as the preferences set out for the corresponding substituentsof a compound of formula (I).

Another group of novel intermediates are compounds of formula (XX)

wherein A¹, A², A³, A⁴, G¹, L, R¹, R², R³, R⁴, Y¹, Y² and Y³ are asdefined for a compound of formula (I); or a salt or N-oxide thereof. Thepreferences for A¹, A², A³, A⁴, G¹, L, R¹, R², R³, R⁴, Y¹, Y² and Y³ arethe same as the preferences set out for the corresponding substituentsof a compound of formula (I).

Another group of novel intermediates are compounds of formula (XXII)

wherein A¹, A², A³, A⁴, L, R¹, R², Y¹, Y² and Y³ are as defined for acompound of formula (I); or a salt or N-oxide thereof. The preferencesfor A¹, A², A³, A⁴, G¹, L, R¹, R², Y¹, Y² and Y³ are the same as thepreferences set out for the corresponding substituents of a compound offormula (I).

Another group of novel intermediates are compounds of formula (XXIII)

wherein A¹, A², A³, A⁴, G¹, L, R¹, R², Y¹, Y² and Y³ are as defined fora compound of formula (I) and Hal is a halogen, such as bromo or chloro;or a salt or N-oxide thereof. The preferences for A¹, A², A³, A⁴, G¹, L,R¹, R², Y¹, Y² and Y³ are the same as the preferences set out for thecorresponding substituents of a compound of formula (I).

Another group of novel intermediates are compounds of formula (XXIV)

wherein A¹, A², A³, A⁴, G¹, L, R¹, R², R³, R⁴, Y¹, Y² and Y³ are asdefined for a compound of formula (I); or a salt or N-oxide thereof. Thepreferences for A¹, A², A³, A⁴, G¹, L, R¹, R², R³, R⁴, Y¹, Y² and Y³ arethe same as the preferences set out for the corresponding substituentsof a compound of formula (I).

Another group of novel intermediates are compounds of formula (XXIV′)

wherein A¹, A², A³, A⁴, G¹, L, R¹, R², R³, R⁴, Y¹, Y² and Y³ are asdefined for a compound of formula (I); or a salt or N-oxide thereof. Thepreferences for A¹, A², A³, A⁴, G¹, L, R¹, R², R³, R⁴, Y¹, Y² and Y³ arethe same as the preferences set out for the corresponding substituentsof a compound of formula (I).

A further embodiment of this invention are compounds of formula (I′)wherein A¹, A², A³ and A⁴ are independently of one another C—H, C—R⁵, ornitrogen; G¹ is oxygen or sulfur;

-   L is a single bond, C₁-C₆alkyl, C₁-C₆haloalkyl, C₂-C₆alkenyl,    C₂-C₆haloalkenyl, C₂-C₆alkynyl, or C₂-C₆haloalkynyl;-   R¹ is hydrogen, C₁-C₆alkyl, C₁-C₆alkylcarbonyl, or    C₁-C₆alkoxycarbonyl;-   R² is hydrogen, or C₁-C₆alkyl;-   R³ is C₁-C₆haloalkyl;-   R⁴ is aryl or aryl substituted by one to three substituents    independently selected from halogen, cyano, nitro, C₁-C₆alkyl,    C₁-C₆haloalkyl, C₁-C₆alkoxy, C₁-C₆haloalkoxy, or    C₁-C₆alkoxycarbonyl, or heterocyclyl or heterocyclyl substituted by    one to three substituents independently selected from halogen,    cyano, nitro, C₁-C₆alkyl, C₁-C₆haloalkyl, C₁-C₆alkoxy,    C₁-C₆haloalkoxy, or C₁-C₆alkoxycarbonyl;-   each R⁵ is independently halogen, cyano, nitro, C₁-C₆alkyl,    C₁-C₆haloalkyl, C₂-C₆alkenyl, C₂-C₆haloalkenyl, C₂-C₆alkynyl,    C₂-C₆haloalkynyl, C₁-C₆alkoxy, C₁-C₆haloalkoxy, or    C₁-C₆alkoxycarbonyl;-   Y¹, Y² and Y³ are independently of another CR⁶R⁷, C═O, C═N—OR⁸,    N—R⁸, S, SO, SO₂, S═N—R⁸, or SO═N—R⁸, provided that at least one of    Y¹, Y² or Y³ is not CR⁶R⁷;-   each R⁶ and R⁷ is independently hydrogen, halogen, C₁-C₆alkyl, or    C₁-C₆haloalkyl; and-   each R⁸ is independently hydrogen, cyano, C₁-C₆alkyl,    C₁-C₆haloalkyl, C₁-C₆alkylcarbonyl, C₁-C₆haloalkylcarbonyl,    C₁-C₆alkoxycarbonyl, C₁-C₆haloalkoxycarbonyl, C₁-C₆alkyl-sulfonyl,    C₁-C₆haloalkylsulfonyl, aryl-C₁-C₄alkyl-, or aryl-C₁-C₄alkyl-    wherein the aryl moiety is substituted by one to three substituents    independently selected from halogen, cyano, nitro, C₁-C₆alkyl,    C₁-C₆haloalkyl, C₁-C₆alkoxy, C₁-C₆haloalkoxy, or    C₁-C₆alkoxycarbonyl, heteroaryl-C₁-C₄alkyl-, or    heteroaryl-C₁-C₄alkyl- wherein the heteroaryl moiety is substituted    by one to three substituents independently selected from halogen,    cyano, nitro, C₁-C₆alkyl, C₁-C₆haloalkyl, C₁-C₆alkoxy,    C₁-C₆haloalkoxy, or C₁-C₆alkoxycarbonyl; or a salt or N-oxide    thereof. The preferences for A¹, A², A³, A⁴, G¹, L, R¹, R², R³, R⁴,    Y¹, Y² and Y³ are the same as the preferences set out for the    corresponding substituents of compounds of the formula (I).

A further embodiment of this invention are compounds of formula (I″)wherein

-   A¹, A², A³ and A⁴ are independently of one another C—H, C—R⁵, or    nitrogen;-   G¹ is oxygen or sulfur;-   L is a single bond, C₁-C₈alkyl, C₁-C₈haloalkyl, C₂-C₈alkenyl,    C₂-C₈haloalkenyl, C₂-C₈alkynyl, or C₂-C₈haloalkynyl;-   R¹ is hydrogen, C₁-C₈alkyl, C₁-C₈alkylcarbonyl-, or    C₁-C₈alkoxycarbonyl-;-   R² is hydrogen, or C₁-C₈alkyl;-   R³ is C₁-C₈haloalkyl;-   R⁴ is aryl or aryl substituted by one to three R⁶, or heterocyclyl    or heterocyclyl substituted by one to three R⁶;-   Y¹, Y² and Y³ are independently of another CR⁷R⁸, C═O, C═N—OR⁹,    N—R⁹, S, SO, SO₂, S═N—R⁹, or SO═N—R⁹, provided that at least one of    Y¹, Y² or Y³ is not CR⁷R⁸;-   each R⁵ is independently halogen, cyano, nitro, C₁-C₈alkyl,    C₁-C₈haloalkyl, C₂-C₈alkenyl, C₂-C₈haloalkenyl, C₂-C₈alkynyl,    C₂-C₈haloalkynyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy,    C₁-C₈alkoxycarbonyl-, aryl or aryl optionally substituted by one to    three R¹⁰, or heteroaryl or heteroaryl optionally substituted by one    to three R¹⁰;-   each R⁶ is independently halogen, cyano, nitro, C₁-C₈alkyl,    C₁-C₈haloalkyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy, or    C₁-C₈alkoxycarbonyl-;-   each R⁷ and R⁸ is independently hydrogen, halogen, C₁-C₈alkyl, or    C₁-C₈haloalkyl;-   each R⁹ is independently hydrogen, cyano, C₁-C₈alkyl,    C₁-C₈haloalkyl, C₁-C₈alkylcarbonyl-, C₁-C₈haloalkylcarbonyl-,    C₁-C₈alkoxycarbonyl-, C₁-C₈haloalkoxycarbonyl-,    C₁-C₈alkyl-sulfonyl-, C₁-C₈haloalkylsulfonyl-, aryl-C₁-C₄alkyl- or    aryl-C₁-C₄alkyl- wherein the aryl moiety is substituted by one to    three R¹¹, or heteroaryl-C₁-C₄alkyl- or heteroaryl-C₁-C₄alkyl-    wherein the heteroaryl moiety is substituted by one to three R¹¹;-   each R¹⁰ is independently halogen, cyano, nitro, C₁-C₈alkyl,    C₁-C₈haloalkyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy, or    C₁-C₈alkoxycarbonyl-; and-   each R¹¹ is independently halogen, cyano, nitro, C₁-C₈alkyl,    C₁-C₈haloalkyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy, or    C₁-C₈alkoxycarbonyl-; or a salt or N-oxide thereof. The preferences    for A¹, A², A³, A⁴, L, R¹, R², R³, R⁴, Y¹, Y² and Y³ are the same as    preferences set out for the corresponding substituents of compounds    of the formula (I).

The compounds in Table 1 to Table 32 below illustrate the compounds ofthe invention.

Table 1:

-   Table 1 provides 8 compounds of formula (Ia) wherein G¹ is oxygen,    R¹ is hydrogen, R⁵ is bromo, Y² is C═O, and R², Y¹ and Y³ have the    values listed in the table below.

(Ia)

Compound numbers R² Y¹ Y³ 1.01 H CH₂ CH₂ 1.02 H CH(Me) CH₂ 1.03 H C(Me)₂CH₂ 1.04 H C(Me)₂ C(Me)₂ 1.05 Me CH₂ CH₂ 1.06 Me CH(Me) CH₂ 1.07 MeC(Me)₂ CH₂ 1.08 Me C(Me)₂ C(Me)₂Table 2:

-   Table 2 provides 8 compounds of formula (Ia) wherein G¹ is oxygen,    R¹ is hydrogen, R⁵ is bromo, Y² is C═N—OMe, and R², Y¹ and Y³ have    the values listed in Table 1.    Table 3:-   Table 3 provides 8 compounds of formula (Ia) wherein G¹ is oxygen,    R¹ is hydrogen, R⁵ is bromo, Y² is N-Me, and R², Y¹ and Y³ have the    values listed in Table 1.    Table 4:-   Table 4 provides 8 compounds of formula (Ia) wherein G¹ is oxygen,    R¹ is hydrogen, R⁵ is bromo, Y² is N—CH₂—C₆H₅, and R², Y¹ and Y³    have the values listed in Table 1.    Table 5:-   Table 5 provides 8 compounds of formula (Ia) wherein G¹ is oxygen,    R¹ is hydrogen, R⁵ is bromo, Y² is S, and R², Y¹ and Y³ have the    values listed in Table 1.    Table 6:-   Table 6 provides 8 compounds of formula (Ia) wherein G¹ is oxygen,    R¹ is hydrogen, R⁵ is bromo, Y² is SO, and R², Y¹ and Y³ have the    values listed in Table 1.    Table 7:-   Table 7 provides 8 compounds of formula (Ia) wherein G¹ is oxygen,    R¹ is hydrogen, R⁵ is bromo, Y² is SO₂, and R², Y¹ and Y³ have the    values listed in Table 1.    Table 8:-   Table 8 provides 8 compounds of formula (Ia) wherein G¹ is oxygen,    R¹ is hydrogen, R⁵ is bromo, Y² is SONH, and R², Y¹ and Y³ have the    values listed in Table 1.    Table 9:-   Table 9 provides 8 compounds of formula (Ia) wherein G¹ is oxygen,    R¹ is hydrogen, R⁵ is cyano, Y² is C═O, and R², Y¹ and Y³ have the    values listed in Table 1.    Table 10:-   Table 10 provides 8 compounds of formula (Ia) wherein G¹ is oxygen,    R¹ is hydrogen, R⁵ is cyano, Y² is C═N—OMe, and R², Y¹ and Y³ have    the values listed in Table 1.    Table 11:-   Table 11 provides 8 compounds of formula (Ia) wherein G¹ is oxygen,    R¹ is hydrogen, R⁵ is cyano, Y² is N-Me, and R², Y¹ and Y³ have the    values listed in Table 1.    Table 12:-   Table 12 provides 8 compounds of formula (Ia) wherein G¹ is oxygen,    R¹ is hydrogen, R⁵ is cyano, Y² is N—CH₂—C₆H₅, and R², Y¹ and Y³    have the values listed in Table 1.    Table 13:-   Table 13 provides 8 compounds of formula (Ia) wherein G¹ is oxygen,    R¹ is hydrogen, R⁵ is cyano, Y² is S, and R², Y¹ and Y³ have the    values listed in Table 1.    Table 14:-   Table 14 provides 8 compounds of formula (Ia) wherein G¹ is oxygen,    R¹ is hydrogen, R⁵ is cyano, Y² is SO, and R², Y¹ and Y³ have the    values listed in Table 1.    Table 15:-   Table 15 provides 8 compounds of formula (Ia) wherein G¹ is oxygen,    R¹ is hydrogen, R⁵ is cyano, Y² is SO₂, and R², Y¹ and Y³ have the    values listed in Table 1.    Table 16:-   Table 16 provides 8 compounds of formula (Ia) wherein G¹ is oxygen,    R¹ is hydrogen, R⁵ is cyano, Y² is SONH, and R², Y¹ and Y³ have the    values listed in Table 1.    Table 17:-   Table 17 provides 8 compounds of formula (Ia) wherein G¹ is oxygen,    R¹ is hydrogen, R⁵ is methyl, Y² is C═O, and R², Y¹ and Y³ have the    values listed in Table 1.    Table 18:-   Table 18 provides 8 compounds of formula (Ia) wherein G¹ is oxygen,    R¹ is hydrogen, R⁵ is methyl, Y² is C═N—OMe, and R², Y¹ and Y³ have    the values listed in Table 1.    Table 19:-   Table 19 provides 8 compounds of formula (Ia) wherein G¹ is oxygen,    R¹ is hydrogen, R⁵ is methyl, Y² is N-Me, and R², Y¹ and Y³ have the    values listed in Table 1.    Table 20:-   Table 20 provides 8 compounds of formula (Ia) wherein G¹ is oxygen,    R¹ is hydrogen, R⁵ is methyl, Y² is N—CH₂—C₆H₅, and R², Y¹ and Y³    have the values listed in Table 1.    Table 21:-   Table 21 provides 8 compounds of formula (Ia) wherein G¹ is oxygen,    R¹ is hydrogen, R⁵ is methyl, Y² is S, and R², Y¹ and Y³ have the    values listed in Table 1.    Table 22:-   Table 22 provides 8 compounds of formula (Ia) wherein G¹ is oxygen,    R¹ is hydrogen, R⁵ is methyl, Y² is SO, and R², Y¹ and Y³ have the    values listed in Table 1.    Table 23:-   Table 23 provides 8 compounds of formula (Ia) wherein G¹ is oxygen,    R¹ is hydrogen, R⁵ is methyl, Y² is SO₂, and R², Y¹ and Y³ have the    values listed in Table 1.    Table 24:-   Table 24 provides 8 compounds of formula (Ia) wherein G¹ is oxygen,    R¹ is hydrogen, R⁵ is methyl, Y² is SONH, and R², Y¹ and Y³ have the    values listed in Table 1.    Table 25:-   Table 25 provides 8 compounds of formula (Ia) wherein G¹ is oxygen,    R¹ is hydrogen, R⁵ is trifluoromethyl, Y² is C═O, and R², Y¹ and Y³    have the values listed in Table 1.    Table 26:-   Table 26 provides 8 compounds of formula (Ia) wherein G¹ is oxygen,    R¹ is hydrogen, R⁵ is trifluoromethyl, Y² is C═N—OMe, and R², Y¹ and    Y³ have the values listed in Table 1.    Table 27:-   Table 27 provides 8 compounds of formula (Ia) wherein G¹ is oxygen,    R¹ is hydrogen, R⁵ is trifluoromethyl, Y² is N-Me, and R², Y¹ and Y³    have the values listed in Table 1.    Table 28:-   Table 28 provides 8 compounds of formula (Ia) wherein G¹ is oxygen,    R¹ is hydrogen, R⁵ is trifluoromethyl, Y² is N—CH₂—C₆H₅, and R², Y¹    and Y³ have the values listed in Table 1.    Table 29:-   Table 29 provides 8 compounds of formula (Ia) wherein G¹ is oxygen,    R¹ is hydrogen, R⁵ is trifluoromethyl, Y² is S, and R², Y¹ and Y³    have the values listed in Table 1.    Table 30:-   Table 30 provides 8 compounds of formula (Ia) wherein G¹ is oxygen,    R¹ is hydrogen, R⁵ is trifluoromethyl, Y² is SO, and R², Y¹ and Y³    have the values listed in Table 1.    Table 31:-   Table 31 provides 8 compounds of formula (Ia) wherein G¹ is oxygen,    R¹ is hydrogen, R⁵ is trifluoromethyl, Y² is SO₂, and R², Y¹ and Y³    have the values listed in Table 1.    Table 32:-   Table 32 provides 8 compounds of formula (Ia) wherein G¹ is oxygen,    R¹ is hydrogen, R⁵ is trifluoromethyl, Y² is SONH, and R², Y¹ and Y³    have the values listed in Table 1.

The compounds of the invention may be made by a variety of methods asshown in Schemes 1 to 7.

1) Compounds of formula (I) wherein G¹ is oxygen, can be prepared byreacting a compound of formula (II) wherein G¹ is oxygen and R is OH,C₁-C₆alkoxy or Cl, F or Br, with an amine of formula (III) as shown inScheme 1. When R is OH such reactions are usually carried out in thepresence of a coupling reagent, such as N,N′-dicyclohexylcarbodiimide(“DCC”), 1-ethyl-3-(3-dimethylamino-propyl)carbodiimide hydrochloride(“EDC”) or bis(2-oxo-3-oxazolidinyl)phosphonic chloride (“BOP-Cl”), inthe presence of a base, and optionally in the presence of a nucleophiliccatalyst, such as hydroxybenzotriazole (“HOBT”). When R is Cl, suchreactions are usually carried out in the presence of a base, andoptionally in the presence of a nucleophilic catalyst. Alternatively, itis possible to conduct the reaction in a biphasic system comprising anorganic solvent, preferably ethyl acetate, and an aqueous solvent,preferably a solution of sodium hydrogen carbonate. When R isC₁-C₆alkoxy it is sometimes possible to convert the ester directly tothe amide by heating the ester and amine together in a thermal process.Suitable bases include pyridine, triethylamine,4-(dimethylamino)-pyridine (“DMAP”) or diisopropylethylamine (Hunig'sbase). Preferred solvents are N,N-dimethylacetamide, tetrahydrofuran,dioxane, 1,2-dimethoxyethane, ethyl acetate and toluene. The reaction iscarried out at a temperature of from 0° C. to 100° C., preferably from15° C. to 30° C., in particular at ambient temperature. Amines offormula (III) are known in the literature or can be prepared usingmethods known to a person skilled in the art.

2) Acid halides of formula (II), wherein G¹ is oxygen and R is Cl, F orBr, may be made from carboxylic acids of formula (II), wherein G¹ isoxygen and R is OH, under standard conditions, such as treatment withthionyl chloride or oxalyl chloride. A preferred solvent isdichloromethane. The reaction is carried out at a temperature of from 0°C. to 100° C., preferably from 15° C. to 30° C., in particular atambient temperature.

3) Carboxylic acids of formula (II), wherein G¹ is oxygen and R is OH,may be formed from esters of formula (II), wherein G¹ is oxygen and R isC₁-C₆alkoxy. It is known to a person skilled in the art that there aremany methods for the hydrolysis of such esters depending on the natureof the alkoxy group. One widely used method to achieve such atransformation is the treatment of the ester with an alkali hydroxide,such as lithium hydroxide, sodium hydroxide or potassium hydroxide, in asolvent, such as ethanol or tetrahydrofuran, in the presence of water.Another is the treatment of the ester with an acid, such astrifluoroacetic acid, in a solvent, such as dichloromethane, followed byaddition of water. The reaction is carried out at a temperature of from0° C. to 150° C., preferably from 15° C. to 100° C., in particular at50° C.

4) Compounds of formula (II) wherein G¹ is oxygen and R is C₁-C₆alkoxy,can be prepared by reacting a compound of formula (IV) wherein X^(B) isa leaving group, for example a halogen, such as bromo, with carbonmonoxide and an alcohol of formula R—OH; such as ethanol, in thepresence of a catalyst, such as bis(triphenylphosphine)palladium(II)dichloride, and a base, such as pyridine, triethylamine,4-(dimethylamino)-pyridine (“DMAP”) or diisopropylethylamine (Hunig'sbase). The reaction is carried out at a temperature of from 50° C. to200° C., preferably from 100° C. to 150° C., in particular at 115° C.The reaction is carried out at a pressure of from 50 to 200 bar,preferably from 100 to 150 bar, in particular at 120 bar.

5) Alternatively, compounds of formula (I) wherein G¹ is oxygen, can beprepared by reacting a compound of formula (IV) wherein X^(B) is aleaving group, for example a halogen, such as bromo, with carbonmonoxide and an amine of formula (III), in the presence of a catalyst,such as palladium(II) acetate or bis(triphenylphosphine)palladium(II)dichloride, optionally in the presence of a ligand, such astriphenylphosphine, and a base, such as sodium carbonate, pyridine,triethylamine, 4-(dimethylamino)-pyridine (“DMAP”) ordiisopropylethylamine (Hunig's base), in a solvent, such as water,N,N-dimethylformamide or tetrahydrofuran. The reaction is carried out ata temperature of from 50° C. to 200° C., preferably from 100° C. to 150°C. The reaction is carried out at a pressure of from 50 to 200 bar,preferably from 100 to 150 bar.

6) Compounds of formula (IV) wherein X^(B) is a leaving group, forexample a halogen, such as bromo, can be made by reaction of an oxime offormula (V) wherein X^(B) is a leaving group, for example a halogen,such as bromo, and a vinyl compound of formula (VI) in a two stepreaction. In the first step, the oxime of formula (V) is reacted with ahalogenating agent, for example a succinimide, such asN-chlorosuccinimide (“NCS”), in the presence of a suitable solvent, forexample a polar solvent, such as N,N-dimethylformamide. The first stepis carried out at a temperature of from 0° C. to 100° C., preferablyfrom 15° C. to 30° C., in particular at ambient temperature.

In the second step, the chloro hydroxy imine intermediate of formula(V′) is reacted with the vinyl compound of formula (VI) in the presenceof a base, for example an organic base, such as triethylamine, or aninorganic base, such as sodium hydrogen carbonate, in the presence of asuitable solvent, for example a polar solvent, such asN,N-dimethylformamide or isopropanol. It is possible to conduct thesetwo steps separately and optionally to isolate the chloro hydroxy imineintermediate (see Example I12 and Example I13) or more conveniently toconduct these two steps successively in one reaction vessel withoutisolation of the intermediate (see Example I3). The second step iscarried out at a temperature of from 0° C. to 100° C., preferably from15° C. to 30° C., in particular at ambient temperature. Vinyl compoundsof formula (VI) are commercially available or can be made by methodsknown to a person skilled in the art.

7) Compounds of formula (V) wherein X^(B) is a leaving group, forexample a halogen, such as bromo, can be made by reaction of an aldehydeof formula (VII) wherein X^(B) is a leaving group, for example ahalogen, such as bromo, with a hydroxylamine, such as hydroxylaminehydrochloride. Such reactions are carried out in the presence of a base,for example an organic base, such as triethylamine or sodium acetate, oran inorganic base, such as sodium hydrogen carbonate, optionally in thepresence of a solvent, for example an alcohol, such as methanol orethanol, or water, or mixtures thereof. The reaction is carried out at atemperature of from 0° C. to 100° C., preferably from 15° C. to 30° C.,in particular at ambient temperature. Aldehydes of formula (VII) arecommercially available or can be made by methods known to a personskilled in the art.

8) Compounds of formula (I) wherein G¹ is oxygen and one of Y¹, Y² andY³ is SO or SO₂ and the remaining Y¹, Y² and Y³ are independently CR⁷R⁸,can be made from a compound of formula (I) wherein G¹ is oxygen and oneof Y¹, Y² and Y³ is S (or SO) and the remaining Y¹, Y² and Y³ areindependently CR⁷R⁸, by treatment with an oxidising reagent, such aspotassium permanganate, 3-chloroperoxybenzoic acid (“MCPBA”), sodiumperiodate/ruthenium(II) oxide, hydrogen peroxide, oxone and sodiumhypochlorite. One equivalent of oxidising reagent is required to conventa sulfide to a sulfoxide, or a sulfoxide to a sulfone. Two equivalentsof oxidising reagent are required to convent a sulfide to a sulfone.Preferred solvents are tetrahydrofuran, dioxane, 1,2-dimethoxyethane,ethyl acetate, toluene, dichloromethane and water, or mixtures thereof.The reaction is optionally carried out in the presence of a base, forexample a carbonate, such as sodium hydrogen carbonate. The reaction iscarried out at a temperature of from 0° C. to 100° C., preferably from15° C. to 30° C., in particular at ambient temperature. Alternatively,these transformations can be carried out on an amine of formula (III) oron a protected form of an amine of formula (III). For protecting groupssuitable for amines, see, for example, Greene's Protective Groups inOrganic Synthesis, 4th Edition, P. G. M. Wuts, T. W. Greene, October2006.

9) Compounds of formula (I) wherein G¹ is oxygen and one of Y¹, Y² andY³ is SO═N—R⁹ and the remaining Y¹, Y² and Y³ are independently CR⁷R⁸,can be made from a compound of formula (I) wherein G¹ is oxygen and oneof Y¹, Y² and Y³ is S═N—R⁹ and the remaining Y¹, Y² and Y³ areindependently CR⁷R⁸, by treatment with an oxidising reagent, such aspotassium permanganate, 3-chloroperoxybenzoic acid (“MCPBA”), sodiumperiodate/ruthenium(II) oxide, hydrogen peroxide, oxone and sodiumhypochlorite. One equivalent of oxidising reagent is required to conventa sulfilimine to a sulfoximine. Preferred solvents are tetrahydrofuran,dioxane, 1,2-dimethoxyethane, ethyl acetate, toluene, dichloromethaneand water, or mixtures thereof. The reaction is optionally carried outin the presence of a base, for example a carbonate, such as sodiumhydrogen carbonate. The reaction is carried out at a temperature of from0° C. to 100° C., preferably from 15° C. to 30° C., in particular atambient temperature. Alternatively, this transformation can be carriedout on an amine of formula (III) or on a protected form of an amine offormula (III). For protecting groups suitable for amines, see, forexample, Greene's Protective Groups in Organic Synthesis, 4th Edition,P. G. M. Wuts, T. W. Greene, October 2006.

10) Compounds of formula (I) wherein G¹ is oxygen and one of Y¹, Y² andY³ is S═N—R⁹ or SO═N—R⁹ and the remaining Y¹, Y² and Y³ areindependently CR⁷R⁸, can be made from a compound of formula (I) whereinG¹ is oxygen and one of Y¹, Y² and Y³ is S or SO, respectively, and theremaining Y¹, Y² and Y³ are independently CR⁷R⁸, by treatment with areagent, such as sodium azide in sulfuric acid,O-mesitylenesulfonylhydroxylamine (“MSH”), or metal-catalyzed methodssuch as R⁹N₃/FeCl₂, PhI═N—R⁹/CuOTf, PhI═N—R⁹/Cu(OTf)₂, PhI═N—R⁹/CuPF₆,PhI(OAc)₂/R⁹—NH₂/MgO/Rh₂(OAc)₄ or oxaziridines (e.g.3-(4-cyano-phenyl)-oxaziridine-2-carboxylic acid tert-butyl ester). Oneequivalent of reagent is required to convert a sulfoxide to asulfoximine, or a sulfide to a sulfilimine. Alternatively, thesetransformations can be carried out on an amine of formula (III) or on aprotected form of an amine of formula (III). For protecting groupssuitable for amines, see, for example, Greene's Protective Groups inOrganic Synthesis, 4th Edition, P. G. M. Wuts, T. W. Greene, October2006.

11) Compounds of formula (I), wherein G¹ is sulfur, may be made bytreatment of a compound of formula (II), wherein G¹ is oxygen and R isOH, C₁-C₆alkoxy or Cl, F or Br, with a thio-transfer reagent such asLawesson's reagent or phosphorus pentasulfide prior to elaborating tocompounds of formula (I), as described under 1).

12) Alternatively, compounds of formula (II) wherein G¹ is oxygen and Ris C₁-C₆alkoxy, such as methoxy or tert-butoxy, can be prepared byreaction of an oxime of formula (VIII) wherein G¹ is oxygen and R isC₁-C₆alkoxy, such as methoxy or tert-butoxy, with a halogenating agentfollowed by a vinyl compound of formula (VI) and base as shown in Scheme2 in a two step reaction as described under 6). The intermediate offormula (VIII′) wherein G¹ is oxygen and R is C₁-C₆alkoxy, such asmethoxy or tert-butoxy, can optionally be isolated (see Example I12).

13) Compounds of formula (VIII) wherein G¹ is oxygen and R isC₁-C₆alkoxy, such as methoxy or tert-butoxy, can be made by reaction ofan aldehyde of formula (IX) wherein G¹ is oxygen and R is C₁-C₆alkoxy,for example methoxy or tert-butoxy, with a hydroxylamine, such ashydroxylamine hydrochloride, as described under 7).

14) Compounds of formula (IX) wherein G¹ is oxygen and R is C₁-C₆alkoxy,such as methoxy or tert-butoxy, can be prepared by reaction of acompound of formula (X) wherein G¹ is oxygen and R is C₁-C₆alkoxy, forexample methoxy or tert-butoxy, and X^(B) is a leaving group, forexample a halogen, such as bromo, with a formylating agent, such asN,N-dimethylformamide. Such reactions are carried out in the presence ofa base, for example a lithium base, such as n-butyl lithium, in thepresence of a suitable solvent, for example a polar solvent, such astetrahydrofuran or excess N,N-dimethylformamide. Compounds of formula(X) wherein G¹ is oxygen and R is C₁-C₆alkoxy, such as methoxy ortert-butoxy, are commercially available or can be made by methods knownto a person skilled in the art.

15) Alternatively, compounds of formula (I) wherein G¹ is oxygen, can beprepared by reaction of an oxime of formula (XI) wherein G¹ is oxygen,with a halogenating agent followed by a vinyl compound of formula (VI)and base as shown in Scheme 3 in a two step reaction as described under6). The intermediate of formula (XI′) wherein G¹ is oxygen, canoptionally be isolated.

16) Compounds of formula (XI) wherein G¹ is oxygen, can be made byreaction of an aldehyde of formula (XII) wherein G¹ is oxygen, with ahydroxylamine, such as hydroxylamine hydrochloride as described under7).

17) Compounds of formula (XII) wherein G¹ is oxygen, can be prepared byreaction of a compound of formula (XIII) wherein G¹ is oxygen and X^(B)is a leaving group, for example a halogen, such as bromo, with aformylating agent, such as N,N-dimethylformamide as described under 13).

18) Compounds of formula (XIII) wherein G¹ is oxygen and X^(B) is aleaving group, for example a halogen, such as bromo, can be prepared byreacting an acid derivative of formula (X) wherein G¹ is oxygen and R isOH, C₁-C₆alkoxy or Cl, F or Br, and X^(B) is a leaving group, forexample a halogen, such as bromo, with an amine of formula (III) asdescribed under 1).

19) Alternatively, compounds of formula (I) wherein G¹ is oxygen, can bemade by reaction of an N-hydroxy-amidine of formula (XIV) wherein G¹ isoxygen, and a vinyl compound of formula (VI) in a two step reaction asshown in Scheme 4. In the first step, the N-hydroxy-amidine of formula(XIV) wherein G¹ is oxygen, is reacted with a nitrosylating agent, suchas sodium nitrite, in the presence of an acid, such as aqueoushydrochloric acid. The first step is carried out at a temperature offrom −20° C. to +30° C., preferably from −5° C. to +10° C.

In the second step, the chloro hydroxy imine intermediate of formula(XI′) wherein G¹ is oxygen, is reacted with the vinyl compound offormula (VI) in the presence of a base, for example an organic base,such as triethylamine, or an inorganic base, such as sodium hydrogencarbonate, in the presence of a suitable solvent, for example a polarsolvent, such as N,N-dimethylformamide or isopropanol. It is possible toconduct these two steps separately and optionally to isolate the chlorohydroxy imine intermediate or more conveniently to conduct these twosteps successively in one reaction vessel without isolation of theintermediate. The second step is carried out at a temperature of from 0°C. to 100° C., preferably from 15° C. to 30° C., in particular atambient temperature.

20) Compounds of formula (XIV) wherein G¹ is oxygen, can be made byreaction of a nitrile of formula (XV) wherein G¹ is oxygen, with ahydroxylamine, such as hydroxylamine hydrochloride as described under7).

21) Compounds of formula (XV) wherein G¹ is oxygen, can be prepared byreacting an acid derivative of formula (XVI) wherein G¹ is oxygen and Ris OH, C₁-C₆alkoxy or Cl, F or Br, with an amine of formula (III) asdescribed under 1). Compounds of formula (XVI) wherein G¹ is oxygen andR is C₁-C₆alkoxy, such as methoxy or tert-butoxy, are commerciallyavailable or can be made by methods known to a person skilled in theart. Alternatively, compounds of formula (XV) wherein G¹ is oxygen, canbe prepared by displacing a leaving group of a compound of formula (XII)wherein G¹ is oxygen, with a cyano group.

22) Alternatively, compounds of formula (I) wherein G¹ is oxygen, can beprepared by cyclisation of a compound of formula (XX) wherein G¹ isoxygen, as shown in Scheme 5. The cyclisation of a compound of formula(XX) can also be referred to as the dehydration of a compound of formula(XX). Such reactions are usually carried out in the presence of an acid,for example an inorganic acid, such as hydrochloric acid or sulfuricacid, or a sulfonic acid, such as methanesulfonic acid, optionally in asolvent such as water, ethanol or tetrahydrofuran, or mixtures thereof.The reaction is carried out at a temperature of from 0° C. to 100° C.,preferably from 40° C. to 80° C. Representative experimental conditionsfor this transformation are described in Synthetic Communications 2003,23, 4163-4171. Alternatively, dehydration can be carried out using adehydrating agent, such as phosphorus pentoxide, in a solvent, such aschloroform, at a temperature of −20° C. to +50°, preferably at 0° C., asdescribed in Journal of Heterocyclic Chemistry 1990, 27, 275.Alternatively, cyclisation can be carried out under Mitsunobu conditionsinvolving treatment of a compound of formula (XX) with a phosphine, suchas triphenylphosphine, and an azodicarboxylate reagent, such as diethylazodicarboxylate, diisopropyl azodicarboxylate or dicyclohexylazodicarboxylate, in a solvent, such as tetrahydrofuran, at atemperature of from 0° C. to 80° C., preferably from 0° C. to ambienttemperature.

23) Compounds of formula (XX) wherein G¹ is oxygen, can be made byreaction of a β-hydroxy ketone of formula (XIX) wherein G¹ is oxygen,with a hydroxylamine, such as hydroxylamine hydrochloride. Suchreactions are carried out optionally in the presence of a base, forexample an organic base, such as triethylamine or sodium acetate, or aninorganic base, such as sodium hydrogen carbonate, optionally in thepresence of a solvent, for example an alcohol, such as methanol orethanol, or water, or mixtures thereof. The reaction is carried out at atemperature of from 0° C. to 100° C., preferably from 15° C. to 30° C.,in particular at ambient temperature.

24) Compounds of formula (XIX) wherein G¹ is oxygen, can be made byaldol-type reaction of a methyl ketone of formula (XVIII) wherein G¹ isoxygen, with a ketone of formula (XXI). Such reactions are usuallycarried out in the presence of a base, such as sodium hydride, lithiumhydride, lithium diisopropylamide or lithium hexamethyldisilazide, in asolvent, such as tetrahydrofuran, at a temperature of from −78° C. to+100° C., preferably from 0° C. to +80° C. Alternatively, the reactioncan be performed using a Lewis acid, such as titanium tetrachloride, andan amine, such as triethylamine, diisopropylethylamine,tetramethylethylenediamine (“TMEDA”) or tributylamine, in a solvent,such as dichloromethane, at a temperature of from −78° C. to ambienttemperature, preferably at −78° C. Representative conditions for such atransformation are given in Tetrahedron Letters 1997, 38, 8727-8730.Ketones of formula (XXI) are commercially available or can be made bymethods known to a person skilled in the art.

25) Compounds of formula (XVIII) wherein G¹ is oxygen, can be made byreacting an acid derivative of formula (XVII) wherein G¹ is oxygen and Ris OH, C₁-C₆alkoxy or Cl, F or Br, with an amine of formula (III) asdescribed under 1).

26) Compounds of formula (XVII) wherein G¹ is oxygen and R isC₁-C₆alkoxy, can be prepared by reacting a compound of formula (X)wherein G¹ is oxygen and X^(B) is a leaving group, for example ahalogen, such as bromo, with an acetylating reagent, such astributyl(1-ethoxyvinyl)tin, ethyl vinyl ether or butyl vinyl ether, in apresence of a catalyst, such as palladium(0)tetrakis(triphenylphosphine), in a solvent, such as tetrahydrofuran ortoluene, at a temperature of from 60° C. to 110° C. The reaction mayafford an intermediate of formula (XVII′) wherein G¹ is oxygen and R′ isC₁-C₆alkyl, which can be hydrolyzed to a compound of formula (XVII)wherein G¹ is oxygen. Alternatively, the reaction may yield a compoundof formula (XVII) wherein G¹ is oxygen, directly.

The hydrolysis of the intermediate of formula (XVII′) wherein G¹ isoxygen, if required, is usually carried out in the presence of an acid,such as hydrochloric acid, in a solvent, such as water or ethyl acetate,or mixtures thereof, at a temperature of from 0° C. to 50° C.,preferably at ambient temperature.

27) Alternatively, compounds of formula (XX) wherein G¹ is oxygen, canbe prepared by reacting a methyl oxime of formula (XXII) wherein G¹ isoxygen, with a ketone of formula (XXI) in an aldol-type reaction asshown in Scheme 6. Such reactions are usually carried out by treatingthe methyl oxime of formula (XXII) wherein G¹ is oxygen, with a base,such as n-butyl lithium, lithium diisopropylamide or lithiumhexamethyldisilazide, in a solvent, such as tetrahydrofuran, at atemperature of from −78° C. to ambient temperature, preferably from −20°C. to 0° C., followed by addition of the ketone of formula (XXI) at atemperature of from −78° C. to 0° C., preferably at 0° C. Representativeconditions for such a transformation can be found in SyntheticCommunications 2003, 23, 4163-4171.

28) Compounds of formula (XXII) wherein G¹ is oxygen, can be made byreaction of a methyl ketone of formula (XVIII) wherein G¹ is oxygen,with a hydroxylamine as described under 23).

29) Alternatively, compounds of formula (I) wherein G¹ is oxygen, can beobtained by reacting an unsaturated ketone of formula (XXIV) wherein G¹is oxygen, with a hydroxylamine, such as hydroxylamine hydrochloride, asshown on Scheme 7. Such reactions can be performed optionally in thepresence of a base, such as sodium hydroxide or potassium hydroxide, ina solvent, such as methanol, ethanol or water, or mixtures thereof, at atemperature of from 0° C. to 100° C., preferably from ambienttemperature to 80° C. Such conditions are described, for example, in J.Indian Chemical Society 1988, 65(9), 640-2. Such reactions mayoptionally lead to novel intermediates of formula (XXIV′)

Such intermediates can be converted into compounds of formula (I) in thepresence of an acid, such as hydrochloric acid or acetic acid, ormixtures thereof, or a base, such as sodium methoxide, optionally in asolvent, such as methanol or diethyl ether, at a temperature of from 0°C. to 100° C. Representative procedures for this reaction are describedin Eur. J. Org. Chem. 2002, p 1919.

30) Compounds of formula (XXIV) wherein G¹ is oxygen, can be obtained byvarious methods. For example, they can be prepared by reacting in afirst step a compound of formula (XXIII) wherein G¹ is oxygen and Hal isa halogen, such as bromo or chloro, with a phosphine, such astriphenylphosphine. Such reactions are usually performed in a solvent,such as toluene, at a temperature of from ambient temperature to 150°C., preferably from 80° C. to 120° C. In a second step, the intermediateis treated with a ketone of formula (XXI) and a base, such as n-butyllithium or triethylamine, in a solvent, such as tetrahydrofuran, at atemperature of from −78° C. to +100° C., preferably from ambienttemperature to +80° C. Such conditions are described, for example, inJournal of Organic Chemistry 2006, 71(9), 3545-3550.

31) Compounds of formula (XXIII) wherein G¹ is oxygen and Hal is ahalogen, such as bromo or chloro, can be prepared by reacting a methylketone of formula (XVIII) wherein G¹ is oxygen, with a halogenatingagent, such as bromine or chlorine, in a solvent, such as acetic acid,at a temperature of from 0° C. to 50° C., preferably from ambienttemperature to 40° C.

The compounds of formula (I) can be used to combat and controlinfestations of insect pests such as Lepidoptera, Diptera, Hemiptera,Thysanoptera, Orthoptera, Dictyoptera, Coleoptera, Siphonaptera,Hymenoptera and Isoptera and also other invertebrate pests, for example,acarine, nematode and mollusc pests. Insects, acarines, nematodes andmolluscs are hereinafter collectively referred to as pests. The pestswhich may be combated and controlled by the use of the inventioncompounds include those pests associated with agriculture (which termincludes the growing of crops for food and fiber products), horticultureand animal husbandry, companion animals, forestry and the storage ofproducts of vegetable origin (such as fruit, grain and timber); thosepests associated with the damage of man-made structures and thetransmission of diseases of man and animals; and also nuisance pests(such as flies).

Examples of pest species which may be controlled by the compounds offormula (I) include: Myzus persicae (aphid), Aphis gossypii (aphid),Aphis fabae (aphid), Lygus spp. (capsids), Dysdercus spp. (capsids),Nilaparvata lugens (planthopper), Nephotettixc incticeps (leafhopper),Nezara spp. (stinkbugs), Euschistus spp. (stinkbugs), Leptocorisa spp.(stinkbugs), Frankliniella occidentalis (thrip), Thrips spp. (thrips),Leptinotarsa decemlineata (Colorado potato beetle), Anthonomus grandis(boll weevil), Aonidiella spp. (scale insects), Trialeurodes spp. (whiteflies), Bemisia tabaci (white fly), Ostrinia nubilalis (European cornborer), Spodoptera littoralis (cotton leafworm), Heliothis virescens(tobacco budworm), Helicoverpa armigera (cotton bollworm), Helicoverpazea (cotton bollworm), Sylepta derogata (cotton leaf roller), Pierisbrassicae (white butterfly), Plutella xylostella (diamond back moth),Agrotis spp. (cutworms), Chilo suppressalis (rice stem borer), Locustamigratoria (locust), Chortiocetes terminifera (locust), Diabrotica spp.(rootworms), Panonychus ulmi (European red mite), Panonychus citri(citrus red mite), Tetranychus urticae (two-spotted spider mite),Tetranychus cinnabarinus (carmine spider mite), Phyllocoptruta oleivora(citrus rust mite), Polyphagotarsonemus latus (broad mite), Brevipalpusspp. (flat mites), Boophilus microplus (cattle tick), Dermacentorvariabilis (American dog tick), Ctenocephalides fells (cat flea),Liriomyza spp. (leafminer), Musca domestica (housefly), Aedes aegypti(mosquito), Anopheles spp. (mosquitoes), Culex spp. (mosquitoes),Lucillia spp. (blowflies), Blattella germanica (cockroach), Periplanetaamericana (cockroach), Blatta orientalis (cockroach), termites of theMastotermitidae (for example Mastotermes spp.), the Kalotermitidae (forexample Neotermes spp.), the Rhinotermitidae (for example Coptotermesformosanus, Reticulitermes flavipes, R. speratu, R. virginicus, R.hesperus, and R. santonensis) and the Termitidae (for exampleGlobitermes sulfureus), Solenopsis geminata (fire ant), Monomoriumpharaonis (pharaoh's ant), Damalinia spp. and Linognathus spp. (bitingand sucking lice), Meloidogyne spp. (root knot nematodes), Globoderaspp. and Heterodera spp. (cyst nematodes), Pratylenchus spp. (lesionnematodes), Rhodopholus spp. (banana burrowing nematodes), Tylenchulusspp. (citrus nematodes), Haemonchus contortus (barber pole worm),Caenorhabditis elegans (vinegar eelworm), Trichostrongylus spp. (gastrointestinal nematodes) and Deroceras reticulatum (slug).

The invention therefore provides a method of combating and controllinginsects, acarines, nematodes or molluscs which comprises applying aninsecticidally, acaricidally, nematicidally or molluscicidally effectiveamount of a compound of formula (I), or a composition containing acompound of formula (I), to a pest, a locus of pest, preferably a plant,or to a plant susceptible to attack by a pest, The compounds of formula(I) are preferably used against insects, acarines or nematodes.

The term “plant” as used herein includes seedlings, bushes and trees.

Crops are to be understood as also including those crops which have beenrendered tolerant to herbicides or classes of herbicides (e.g. ALS-,GS-, EPSPS-, PPO- and HPPD-inhibitors) by conventional methods ofbreeding or by genetic engineering. An example of a crop that has beenrendered tolerant to imidazolinones, e.g. imazamox, by conventionalmethods of breeding is Clearfield® summer rape (canola). Examples ofcrops that have been rendered tolerant to herbicides by geneticengineering methods include e.g. glyphosate- and glufosinate-resistantmaize varieties commercially available under the trade namesRoundupReady® and LibertyLink®.

Crops are also to be understood as being those which have been renderedresistant to harmful insects by genetic engineering methods, for exampleBt maize (resistant to European corn borer), Bt cotton (resistant tocotton boll weevil) and also Bt potatoes (resistant to Colorado beetle).Examples of Bt maize are the Bt 176 maize hybrids of NK® (SyngentaSeeds). Examples of transgenic plants comprising one or more genes thatcode for an insecticidal resistance and express one or more toxins areKnockOut® (maize), Yield Gard® (maize), NuCOTIN33B® (cotton), Bollgard®(cotton), NewLeaf® (potatoes), NatureGard® and Protexcta®.

Plant crops or seed material thereof can be both resistant to herbicidesand, at the same time, resistant to insect feeding (“stacked” transgenicevents). For example, seed can have the ability to express aninsecticidal Cry3 protein while at the same time being tolerant toglyphosate.

Crops are also to be understood as being those which are obtained byconventional methods of breeding or genetic engineering and containso-called output traits (e.g. improved storage stability, highernutritional value and improved flavor).

In order to apply a compound of formula (I) as an insecticide,acaricide, nematicide or molluscicide to a pest, a locus of pest, or toa plant susceptible to attack by a pest, a compound of formula (I) isusually formulated into a composition which includes, in addition to thecompound of formula (I), a suitable inert diluent or carrier and,optionally, a surface active agent (SFA). SFAs are chemicals which areable to modify the properties of an interface (for example,liquid/solid, liquid/air or liquid/liquid interfaces) by lowering theinterfacial tension and thereby leading to changes in other properties(for example dispersion, emulsification and wetting). It is preferredthat all compositions (both solid and liquid formulations) comprise, byweight, 0.0001 to 95%, more preferably 1 to 85%, for example 5 to 60%,of a compound of formula (I). The composition is generally used for thecontrol of pests such that a compound of formula (I) is applied at arate of from 0.1 g to 10 kg per hectare, preferably from 1 g to 6 kg perhectare, more preferably from 1 g to 1 kg per hectare.

When used in a seed dressing, a compound of formula (I) is used at arate of 0.0001 g to 10 g (for example 0.001 g or 0.05 g), preferably0.005 g to 10 g, more preferably 0.005 g to 4 g, per kilogram of seed.

In another aspect the present invention provides an insecticidal,acaricidal, nematicidal or molluscicidal composition comprising aninsecticidally, acaricidally, nematicidally or molluscicidally effectiveamount of a compound of formula (I) and a suitable carrier or diluenttherefor. The composition is preferably an insecticidal, acaricidal,nematicidal or molluscicidal composition.

The compositions can be chosen from a number of formulation types,including dustable powders (DP), soluble powders (SP), water solublegranules (SG), water dispersible granules (WG), wettable powders (WP),granules (GR) (slow or fast release), soluble concentrates (SL), oilmiscible liquids (OL), ultra low volume liquids (UL), emulsifiableconcentrates (EC), dispersible concentrates (DC), emulsions (both oil inwater (EW) and water in oil (EO)), micro-emulsions (ME), suspensionconcentrates (SC), aerosols, fogging/smoke formulations, capsulesuspensions (CS) and seed treatment formulations. The formulation typechosen in any instance will depend upon the particular purpose envisagedand the physical, chemical and biological properties of the compound offormula (I).

Dustable powders (DP) may be prepared by mixing a compound of formula(I) with one or more solid diluents (for example natural clays, kaolin,pyrophyllite, bentonite, alumina, montmorillonite, kieselguhr, chalk,diatomaceous earths, calcium phosphates, calcium and magnesiumcarbonates, sulfur, lime, flours, talc and other organic and inorganicsolid carriers) and mechanically grinding the mixture to a fine powder.

Soluble powders (SP) may be prepared by mixing a compound of formula (I)with one or more water-soluble inorganic salts (such as sodiumbicarbonate, sodium carbonate or magnesium sulfate) or one or morewater-soluble organic solids (such as a polysaccharide) and, optionally,one or more wetting agents, one or more dispersing agents or a mixtureof said agents to improve water dispersibility/solubility. The mixtureis then ground to a fine powder. Similar compositions may also begranulated to form water soluble granules (SG).

Wettable powders (WP) may be prepared by mixing a compound of formula(I) with one or more solid diluents or carriers, one or more wettingagents and, preferably, one or more dispersing agents and, optionally,one or more suspending agents to facilitate the dispersion in liquids.The mixture is then ground to a fine powder. Similar compositions mayalso be granulated to form water dispersible granules (WG).

Granules (GR) may be formed either by granulating a mixture of acompound of formula (I) and one or more powdered solid diluents orcarriers, or from pre-formed blank granules by absorbing a compound offormula (I) (or a solution thereof, in a suitable agent) in a porousgranular material (such as pumice, attapulgite clays, fuller's earth,kieselguhr, diatomaceous earths or ground corn cobs) or by adsorbing acompound of formula (I) (or a solution thereof, in a suitable agent) onto a hard core material (such as sands, silicates, mineral carbonates,sulfates or phosphates) and drying if necessary. Agents which arecommonly used to aid absorption or adsorption include solvents (such asaliphatic and aromatic petroleum solvents, alcohols, ethers, ketones andesters) and sticking agents (such as polyvinyl acetates, polyvinylalcohols, dextrins, sugars and vegetable oils). One or more otheradditives may also be included in granules (for example an emulsifyingagent, wetting agent or dispersing agent).

Dispersible Concentrates (DC) may be prepared by dissolving a compoundof formula (I) in water or an organic solvent, such as a ketone, alcoholor glycol ether. These solutions may contain a surface active agent (forexample to improve water dilution or prevent crystallization in a spraytank).

Emulsifiable concentrates (EC) or oil-in-water emulsions (EW) may beprepared by dissolving a compound of formula (I) in an organic solvent(optionally containing one or more wetting agents, one or moreemulsifying agents or a mixture of said agents). Suitable organicsolvents for use in ECs include aromatic hydrocarbons (such asalkylbenzenes or alkylnaphthalenes, exemplified by SOLVESSO 100,SOLVESSO 150 and SOLVESSO 200; SOLVESSO is a Registered Trade Mark),ketones (such as cyclohexanone or methylcyclohexanone) and alcohols(such as benzyl alcohol, furfuryl alcohol or butanol),N-alkylpyrrolidones (such as N-methylpyrrolidone or N-octylpyrrolidone),dimethyl amides of fatty acids (such as C₈-C₁₀ fatty acid dimethylamide)and chlorinated hydrocarbons. An EC product may spontaneously emulsifyon addition to water, to produce an emulsion with sufficient stabilityto allow spray application through appropriate equipment. Preparation ofan EW involves obtaining a compound of formula (I) either as a liquid(if it is not a liquid at room temperature, it may be melted at areasonable temperature, typically below 70° C.) or in solution (bydissolving it in an appropriate solvent) and then emulsifiying theresultant liquid or solution into water containing one or more SFAs,under high shear, to produce an emulsion. Suitable solvents for use inEWs include vegetable oils, chlorinated hydrocarbons (such aschlorobenzenes), aromatic solvents (such as alkylbenzenes oralkylnaphthalenes) and other appropriate organic solvents which have alow solubility in water.

Microemulsions (ME) may be prepared by mixing water with a blend of oneor more solvents with one or more SFAs, to produce spontaneously athermodynamically stable isotropic liquid formulation. A compound offormula (I) is present initially in either the water or the solvent/SFAblend. Suitable solvents for use in MEs include those hereinbeforedescribed for use in ECs or in EWs. An ME may be either an oil-in-wateror a water-in-oil system (which system is present may be determined byconductivity measurements) and may be suitable for mixing water-solubleand oil-soluble pesticides in the same formulation. An ME is suitablefor dilution into water, either remaining as a microemulsion or forminga conventional oil-in-water emulsion.

Suspension concentrates (SC) may comprise aqueous or non-aqueoussuspensions of finely divided insoluble solid particles of a compound offormula (I). SCs may be prepared by ball or bead milling the solidcompound of formula (I) in a suitable medium, optionally with one ormore dispersing agents, to produce a fine particle suspension of thecompound. One or more wetting agents may be included in the compositionand a suspending agent may be included to reduce the rate at which theparticles settle. Alternatively, a compound of formula (I) may be drymilled and added to water, containing agents hereinbefore described, toproduce the desired end product.

Aerosol formulations comprise a compound of formula (I) and a suitablepropellant (for example n-butane). A compound of formula (I) may also bedissolved or dispersed in a suitable medium (for example water or awater miscible liquid, such as n-propanol) to provide compositions foruse in non-pressurized, hand-actuated spray pumps.

A compound of formula (I) may be mixed in the dry state with apyrotechnic mixture to form a composition suitable for generating, in anenclosed space, a smoke containing the compound.

Capsule suspensions (CS) may be prepared in a manner similar to thepreparation of EW formulations but with an additional polymerizationstage such that an aqueous dispersion of oil droplets is obtained, inwhich each oil droplet is encapsulated by a polymeric shell and containsa compound of formula (I) and, optionally, a carrier or diluenttherefor. The polymeric shell may be produced by either an interfacialpolycondensation reaction or by a coacervation procedure. Thecompositions may provide for controlled release of the compound offormula (I) and they may be used for seed treatment. A compound offormula (I) may also be formulated in a biodegradable polymeric matrixto provide a slow, controlled release of the compound.

A composition may include one or more additives to improve thebiological performance of the composition (for example by improvingwetting, retention or distribution on surfaces; resistance to rain ontreated surfaces; or uptake or mobility of a compound of formula (I)).Such additives include surface active agents, spray additives based onoils, for example certain mineral oils or natural plant oils (such assoy bean and rape seed oil), and blends of these with otherbio-enhancing adjuvants (ingredients which may aid or modify the actionof a compound of formula (I)).

A compound of formula (I) may also be formulated for use as a seedtreatment, for example as a powder composition, including a powder fordry seed treatment (DS), a water soluble powder (SS) or a waterdispersible powder for slurry treatment (WS), or as a liquidcomposition, including a flowable concentrate (FS), a solution (LS) or acapsule suspension (CS). The preparations of DS, SS, WS, FS and LScompositions are very similar to those of, respectively, DP, SP, WP, SCand DC compositions described above. Compositions for treating seed mayinclude an agent for assisting the adhesion of the composition to theseed (for example a mineral oil or a film-forming barrier).

Wetting agents, dispersing agents and emulsifying agents may be surfaceSFAs of the cationic, anionic, amphoteric or non-ionic type.

Suitable SFAs of the cationic type include quaternary ammonium compounds(for example cetyltrimethyl ammonium bromide), imidazolines and aminesalts.

Suitable anionic SFAs include alkali metals salts of fatty acids, saltsof aliphatic monoesters of sulfuric acid (for example sodium laurylsulfate), salts of sulfonated aromatic compounds (for example sodiumdodecylbenzenesulfonate, calcium dodecylbenzenesulfonate,butylnaphthalene sulfonate and mixtures of sodium di-isopropyl- andtri-isopropyl-naphthalene sulfonates), ether sulfates, alcohol ethersulfates (for example sodium laureth-3-sulfate), ether carboxylates (forexample sodium laureth-3-carboxylate), phosphate esters (products fromthe reaction between one or more fatty alcohols and phosphoric acid(predominately mono-esters) or phosphorus pentoxide (predominatelydi-esters), for example the reaction between lauryl alcohol andtetraphosphoric acid; additionally these products may be ethoxylated),sulfosuccinamates, paraffin or olefine sulfonates, taurates andlignosulfonates.

Suitable SFAs of the amphoteric type include betaines, propionates andglycinates.

Suitable SFAs of the non-ionic type include condensation products ofalkylene oxides, such as ethylene oxide, propylene oxide, butylene oxideor mixtures thereof, with fatty alcohols (such as oleyl alcohol or cetylalcohol) or with alkylphenols (such as octylphenol, nonylphenol oroctylcresol); partial esters derived from long chain fatty acids orhexitol anhydrides; condensation products of said partial esters withethylene oxide; block polymers (comprising ethylene oxide and propyleneoxide); alkanolamides; simple esters (for example fatty acidpolyethylene glycol esters); amine oxides (for example lauryl dimethylamine oxide); and lecithins.

Suitable suspending agents include hydrophilic colloids (such aspolysaccharides, polyvinylpyrrolidone or sodium carboxymethylcellulose)and swelling clays (such as bentonite or attapulgite).

A compound of formula (I) may be applied by any of the known means ofapplying pesticidal compounds. For example, it may be applied,formulated or unformulated, to the pests or to a locus of the pests(such as a habitat of the pests, or a growing plant liable toinfestation by the pests) or to any part of the plant, including thefoliage, stems, branches or roots, to the seed before it is planted orto other media in which plants are growing or are to be planted (such assoil surrounding the roots, the soil generally, paddy water orhydroponic culture systems), directly or it may be sprayed on, dustedon, applied by dipping, applied as a cream or paste formulation, appliedas a vapor or applied through distribution or incorporation of acomposition (such as a granular composition or a composition packed in awater-soluble bag) in soil or an aqueous environment.

A compound of formula (I) may also be injected into plants or sprayedonto vegetation using electrodynamic spraying techniques or other lowvolume methods, or applied by land or aerial irrigation systems.

Compositions for use as aqueous preparations (aqueous solutions ordispersions) are generally supplied in the form of a concentratecontaining a high proportion of the active ingredient, the concentratebeing added to water before use. These concentrates, which may includeDCs, SCs, ECs, EWs, MEs, SGs, SPs, WPs, WGs and CSs, are often requiredto withstand storage for prolonged periods and, after such storage, tobe capable of addition to water to form aqueous preparations whichremain homogeneous for a sufficient time to enable them to be applied byconventional spray equipment. Such aqueous preparations may containvarying amounts of a compound of formula (I) (for example 0.0001 to 10%,by weight) depending upon the purpose for which they are to be used.

A compound of formula (I) may be used in mixtures with fertilizers (forexample nitrogen-, potassium- or phosphorus-containing fertilizers).Suitable formulation types include granules of fertilizer. The mixturespreferably contain up to 25% by weight of the compound of formula (I).

The invention therefore also provides a fertilizer compositioncomprising a fertilizer and a compound of formula (I).

The compositions of this invention may contain other compounds havingbiological activity, for example micronutrients or compounds havingfungicidal activity or which possess plant growth regulating,herbicidal, insecticidal, nematicidal or acaricidal activity.

The compound of formula (I) may be the sole active ingredient of thecomposition or it may be admixed with one or more additional activeingredients such as a pesticide, fungicide, synergist, herbicide orplant growth regulator where appropriate. An additional activeingredient may: provide a composition having a broader spectrum ofactivity or increased persistence at a locus; synergize the activity orcomplement the activity (for example by increasing the speed of effector overcoming repellency) of the compound of formula (I); or help toovercome or prevent the development of resistance to individualcomponents. The particular additional active ingredient will depend uponthe intended utility of the composition. Examples of suitable pesticidesinclude the following:

-   a) Pyrethroids, such as permethrin, cypermethrin, fenvalerate,    esfenvalerate, deltamethrin, cyhalothrin (in particular    lambda-cyhalothrin), bifenthrin, fenpropathrin, cyfluthrin,    tefluthrin, fish safe pyrethroids (for example ethofenprox), natural    pyrethrin, tetramethrin, S-bioallethrin, fenfluthrin, prallethrin or    5-benzyl-3-furylmethyl-(E)-(1R,3S)-2,2-dimethyl-3-(2-oxothiolan-3-ylidenemethyl)cyclopropane    carboxylate;-   b) Organophosphates, such as profenofos, sulprofos, acephate, methyl    parathion, azinphos-methyl, demeton-s-methyl, heptenophos,    thiometon, fenamiphos, monocrotophos, profenofos, triazophos,    methamidophos, dimethoate, phosphamidon, malathion, chlorpyrifos,    phosalone, terbufos, fensulfothion, fonofos, phorate, phoxim,    pirimiphos-methyl, pirimiphos-ethyl, fenitrothion, fosthiazate or    diazinon;-   c) Carbamates (including aryl carbamates), such as pirimicarb,    triazamate, cloethocarb, carbofuran, furathiocarb, ethiofencarb,    aldicarb, thiofurox, carbosulfan, bendiocarb, fenobucarb, propoxur,    methomyl or oxamyl;-   d) Benzoyl ureas, such as diflubenzuron, triflumuron, hexaflumuron,    flufenoxuron or chlorfluazuron;-   e) Organic tin compounds, such as cyhexatin, fenbutatin oxide or    azocyclotin;-   f) Pyrazoles, such as tebufenpyrad and fenpyroximate;-   g) Macrolides, such as avermectins or milbemycins, for example    abamectin, emamectin benzoate, ivermectin, milbemycin, spinosad,    azadirachtin or spinetoram;-   h) Hormones or pheromones;-   i) Organochlorine compounds, such as endosulfan (in particular    alpha-endosulfan), benzene hexachloride, DDT, chlordane or dieldrin;-   j) Amidines, such as chlordimeform or amitraz;-   k) Fumigant agents, such as chloropicrin, dichloropropane, methyl    bromide or metam;-   l) Neonicotinoid compounds, such as imidacloprid, thiacloprid,    acetamiprid, nitenpyram, dinotefuran, thiamethoxam, clothianidin,    nithiazine or flonicamid;-   m) Diacylhydrazines, such as tebufenozide, chromafenozide or    methoxyfenozide;-   n) Diphenyl ethers, such as diofenolan or pyriproxifen;-   o) Indoxacarb;-   p) Chlorfenapyr;-   q) Pymetrozine;-   r) Spirotetramat, spirodiclofen or spiromesifen;-   s) Diamides, such as flubendiamide, chlorantraniliprole (Rynaxypyr®)    or cyantraniliprole;-   t) Sulfoxaflor; or-   u) Metaflumizone.

In addition to the major chemical classes of pesticide listed above,other pesticides having particular targets may be employed in thecomposition, if appropriate for the intended utility of the composition.For instance, selective insecticides for particular crops, for examplestemborer specific insecticides (such as cartap) or hopper specificinsecticides (such as buprofezin) for use in rice may be employed.Alternatively insecticides or acaricides specific for particular insectspecies/stages may also be included in the compositions (for exampleacaricidal ovo-larvicides, such as clofentezine, flubenzimine,hexythiazox or tetradifon; acaricidal motilicides, such as dicofol orpropargite; acaricides, such as bromopropylate or chlorobenzilate; orgrowth regulators, such as hydramethylnon, cyromazine, methoprene,chlorfluazuron or diflubenzuron).

Examples of fungicidal compounds which may be included in thecomposition of the invention are(E)-N-methyl-2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxy-iminoacetamide(SSF-129),4-bromo-2-cyano-N,N-dimethyl-6-trifluoromethylbenzimidazole-1-sulfonamide,α-[N-(3-chloro-2,6-xylyl)-2-methoxyacetamido]-γ-butyrolactone,4-chloro-2-cyano-N,N-dimethyl-5-p-tolylimidazole-1-sulfonamide (IKF-916,cyamidazosulfamid),3-5-dichloro-N-(3-chloro-1-ethyl-1-methyl-2-oxopropyl)-4-methylbenzamide(RH-7281, zoxamide),N-allyl-4,5,-dimethyl-2-trimethylsilylthiophene-3-carboxamide(MON65500),N-(1-cyano-1,2-dimethylpropyl)-2-(2,4-dichlorophenoxy)propionamide(AC382042), N-(2-methoxy-5-pyridyl)-cyclopropane carboxamide,acibenzolar (CGA245704), alanycarb, aldimorph, anilazine, azaconazole,azoxystrobin, benalaxyl, benomyl, biloxazol, bitertanol, blasticidin S,bromuconazole, bupirimate, captafol, captan, carbendazim, carbendazimchlorhydrate, carboxin, carpropamid, carvone, CGA⁴¹³⁹⁶, CGA⁴¹³⁹⁷,chinomethionate, chlorothalonil, chlorozolinate, clozylacon, coppercontaining compounds such as copper oxychloride, copper oxyquinolate,copper sulfate, copper tallate and Bordeaux mixture, cymoxanil,cyproconazole, cyprodinil, debacarb, di-2-pyridyl disulfide1,1′-dioxide, dichlofluanid, diclomezine, dicloran, diethofencarb,difenoconazole, difenzoquat, diflumetorim, O,O-di-iso-propyl-S-benzylthiophosphate, dimefluazole, dimetconazole, dimethomorph, dimethirimol,diniconazole, dinocap, dithianon, dodecyl dimethyl ammonium chloride,dodemorph, dodine, doguadine, edifenphos, epoxiconazole, ethirimol,ethyl(Z)—N-benzyl-N-([methyl(methyl-thioethylideneaminooxycarbonyl)amino]thio)-β-alaninate,etridiazole, famoxadone, fenamidone (RPA407213), fenarimol,fenbuconazole, fenfuram, fenhexamid (KBR2738), fenpiclonil, fenpropidin,fenpropimorph, fentin acetate, fentin hydroxide, ferbam, ferimzone,fluazinam, fludioxonil, flumetover, fluoroimide, fluquinconazole,flusilazole, flutolanil, flutriafol, folpet, fuberidazole, furalaxyl,furametpyr, guazatine, hexaconazole, hydroxyisoxazole, hymexazole,imazalil, imibenconazole, iminoctadine, iminoctadine triacetate,ipconazole, iprobenfos, iprodione, iprovalicarb (SZX0722), isopropanylbutyl carbamate, isoprothiolane, kasugamycin, kresoxim-methyl, LY186054,LY211795, LY248908, mancozeb, maneb, mefenoxam, mepanipyrim, mepronil,metalaxyl, metconazole, metiram, metiram-zinc, metominostrobin,myclobutanil, neoasozin, nickel dimethyldithiocarbamate,nitrothal-isopropyl, nuarimol, ofurace, organomercury compounds,oxadixyl, oxasulfuron, oxolinic acid, oxpoconazole, oxycarboxin,pefurazoate, penconazole, pencycuron, phenazin oxide, phosetyl-A1,phosphorus acids, phthalide, picoxystrobin (ZA1963), polyoxin D,polyram, probenazole, prochloraz, procymidone, propamocarb,propiconazole, propineb, propionic acid, pyrazophos, pyrifenox,pyrimethanil, pyroquilon, pyroxyfur, pyrrolnitrin, quaternary ammoniumcompounds, quinomethionate, quinoxyfen, quintozene, sipconazole (F-155),sodium pentachlorophenate, spiroxamine, streptomycin, sulfur,tebuconazole, tecloftalam, tecnazene, tetraconazole, thiabendazole,thifluzamid, 2-(thiocyanomethylthio)benzothiazole, thiophanate-methyl,thiram, timibenconazole, tolclofos-methyl, tolylfluanid, triadimefon,triadimenol, triazbutil, triazoxide, tricyclazole, tridemorph,trifloxystrobin (CGA279202), triforine, triflumizole, triticonazole,validamycin A, vapam, vinclozolin, zineb and ziram.

The compounds of formula (I) may be mixed with soil, peat or otherrooting media for the protection of plants against seed-borne,soil-borne or foliar fungal diseases.

Examples of suitable synergists for use in the compositions includepiperonyl butoxide, sesamex, safroxan and dodecyl imidazole.

Suitable herbicides and plant-growth regulators for inclusion in thecompositions will depend upon the intended target and the effectrequired.

An example of a rice selective herbicide which may be included ispropanil. An example of a plant growth regulator for use in cotton isPIX™.

Some mixtures may comprise active ingredients which have significantlydifferent physical, chemical or biological properties such that they donot easily lend themselves to the same conventional formulation type. Inthese circumstances other formulation types may be prepared. Forexample, where one active ingredient is a water insoluble solid and theother a water insoluble liquid, it may nevertheless be possible todisperse each active ingredient in the same continuous aqueous phase bydispersing the solid active ingredient as a suspension (using apreparation analogous to that of an SC) but dispersing the liquid activeingredient as an emulsion (using a preparation analogous to that of anEW). The resultant composition is a suspoemulsion (SE) formulation.

The following Examples illustrate, but do not limit, the invention.

PREPARATION EXAMPLES Example I1 Preparation of4-bromo-3-methyl-benzaldehyde

A solution of 4-bromo-3-methyl-benzonitrile (commercially available)(500 mg) in dichloromethane was added at 0° C. to a solution ofdiisobutylaluminium hydride (“DIBAL-H”) (2.6.ml) in hexanes (1M). Themixture was stirred at 0° C. for 2 hours. The reaction mixture waspoured on a mixture of ice (10 g) and aqueous hydrobromic acid (6M) (10ml). The mixture was allowed to warm to ambient temperature and thenextracted twice with dichloromethane. The combined organic phases werewashed with water, dried over sodium sulfate, and concentrated to give4-bromo-3-methyl-benzaldehyde (0.419 g) as a colorless oil. ¹H-NMR (400MHz, CDCl₃): 9.95 (s, 1H), 7.72 (m, 2H), 7.55 (d, 1H), 2.50 (s, 3H) ppm.

Example I2 Preparation of 4-bromo-3-methyl-benzaldehyde oxime

To a solution of 4-bromo-3-methyl-benzaldehyde (4.3 g) (Example I1) inethanol (50 ml), were added at ambient temperature hydroxylaminehydrochloride (1.75 g), sodium acetate (2.07 g) and water (15 ml). Thereaction mixture was stirred at ambient temperature for 3 hours. Thereaction mixture was concentrated and the residue diluted with ethylacetate and aqueous sodium hydroxide (2M). The phases were separated andthe organic phase was washed with brine, dried over sodium sulfate, andconcentrated. The residue was purified by chromatography on silica gel(eluent: cyclohexane/ethyl acetate 4:1) to give4-bromo-3-methyl-benzaldehyde oxime (3.65 g) as a white solid. ¹H-NMR(400 MHz, CDCl₃): 8.05 (s, 1H), 7.50 (m, 2H), 7.25 (d, 1H), 2.40 (s, 3H)ppm.

Example I3 Preparation of3-(4-bromo-3-methyl-phenyl)-5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazole

4-Bromo-3-methyl-benzaldehyde oxime (1.3 g) (Example I2) andN-chlorosuccinimide (“NCS”) (1.8 g) were dissolved inN,N-dimethylformamide (15 ml). The reaction mixture was stirred atambient temperature for 90 minutes. A solution of1,3-dichloro-5-(1-trifluoromethyl-vinyl)-benzene (1.3 g) (preparedaccording to WO 2005/085216) and triethylamine (1.9 ml) inN,N-dimethylformamide (15 ml) was added and the reaction mixture wasstirred at ambient temperature for 18 hours. The reaction mixture wasdiluted with water and ethyl acetate and the phases were separated. Theorganic phase was washed twice with water and the aqueous phases wereextracted twice with ethyl acetate. The combined organic phases weredried over sodium sulfate and concentrated. The residue was purified bychromatography on silica gel (eluent: cyclohexane/dichloromethane 4:1)to give3-(4-bromo-3-methyl-phenyl)-5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazole(1.57 g). ¹H-NMR (400 MHz, CDCl₃): 7.40 (m, 6H), 4.05 (d, 1H), 3.65 (d,1H), 2.40 (s, 3H) ppm.

Example I4 Preparation of4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid ethyl ester

Triethylamine (1.2 ml) was added at ambient temperature to a solution of3-(4-bromo-3-methyl-phenyl)-5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazole(1.2 g) (Example I3) in ethanol (45 ml).Bis(triphenylphosphine)palladium(II) dichloride (“PdCl₂(PPh₃)₂”) (0.185g) was added and the reaction mixture was stirred in a pressure reactorin an atmosphere of carbon monoxide (120 bar) at 115° C. for 8 hours.The reaction mixture was cooled to ambient temperature, filtered overCelite® and concentrated. The residue was purified by preparative HPLCto give4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid ethyl ester (0.85 g) as a yellow oil. ¹H-NMR (CDCl₃, 400 MHz): 7.95(d, 1H), 7.55 (m, 4H), 7.45 (s, 1H), 4.40 (q, 2H), 4.10 (d, 1H), 3.7 (d,1H), 2.60 (s, 3H), 1.40 (t, 3H) ppm.

Example I5 Preparation of4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid

Lithium hydroxide (51 mg) was added at ambient temperature to a solutionof4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid ethyl ester (0.27 g) (Example I4) in tetrahydrofuran (3 ml) andwater (0.75 ml). The reaction mixture was stirred at 50° C. for 18hours. The reaction mixture was cooled to ambient temperature anddiluted with water, acidified by addition of aqueous hydrochloric acid(2M) and extracted three times with ethyl acetate. The combined organicphases were washed with brine, dried over sodium sulfate andconcentrated to give4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid (0.25 g), which was used without further purification. ¹H-NMR(DMSO-d6, 400 MHz): 13.1 (s, 1H), 7.90 (d, 1H), 7.80 (s, 1H), 7.65 (m,4H), 4.40 (m, 2H), 2.55 (s, 3H).

Example I6 Preparation of4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid methyl ester

To a suspension4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid (Example I5) (10 g) in toluene (150 ml) and dimethylformamide (0.1ml) at ambient temperature was added dropwise thionyl chloride (3.5 ml).The reaction mixture was stirred at 50° C. for 2 hours. The solution wasthen cooled to 0° C. and methanol (2 ml) added slowly. The reactionmixture was stirred at ambient temperature for 1 hour. The reactionmixture was concentrated and aqueous sodium hydrogen carbonate(saturated) (50 ml) added to the residue. The mixture was extracted withethyl acetate (3×100 ml). The combined organic extracts were dried oversodium sulfate and concentrated to afford4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid methyl ester as a yellow solid (11.5 g). ¹H-NMR (CDCl₃, 400 MHz):7.95 (d, 1H), 7.55 (m, 4H), 7.45 (s, 1H), 4.10 (d, 1H), 3.90 (s, 3H),3.70 (d, 1H), 2.60 (s, 3H) ppm.

Example I7 Preparation of 4-bromomethyl-2-trifluoromethyl-benzoic acid

A suspension of 4-methyl-2-trifluoromethyl-benzoic acid (commerciallyavailable) (20.242 g), N-bromosuccinimide (“NBS”) (19.52 g) and2,2′-azobis-(2-methylpropanenitrile) (“AIBN”) (0.859 g) inα,α,α-trifluorotoluene (160 ml) was heated to 90° C. for 1.5 hours. Thereaction mixture was allowed to cool to ambient temperature and thendiluted with ethyl acetate (200 ml) and aqueous hydrochloric acid (1M)(100 ml). The phases were separated and the organic phase was washedwith aqueous hydrochloric acid (1M) (100 ml) and brine (150 ml), driedover sodium sulfate and concentrated. The residue was triturated withdichloromethane (40 ml). The solids were isolated by filtration anddried to give 4-bromomethyl-2-trifluoromethyl-benzoic acid (5.01 g) as awhite powder. The filtrate was concentrated, re-dissolved inheptane/dichloromethane (1:1) (40 ml) and the dichloromethane slowlyevaporated to initiate crystallization. The solids were isolated byfiltration, rinsed with pentane and dried to give a second fraction of4-bromomethyl-2-trifluoromethyl-benzoic acid (7.00 g) as a white powder.¹H-NMR (CDCl₃, 400 MHz): 11.5 (br s, 1H), 8.03-7.20 (m, 3H), 4.52 (s,2H).

Similarly, 2-bromo-4-bromomethyl-benzoic acid was obtained from2-bromo-4-methyl-benzoic acid (commercially available). ¹H-NMR (DMSO-d6,400 MHz): 13.54 (br s, 1H), 7.86-7.56 (m, 3H), 4.76 (s, 2H).

Example I8 Preparation of 4-hydroxymethyl-2-trifluoromethyl-benzoic acid

To a suspension of 4-bromomethyl-2-trifluoromethyl-benzoic acid (ExampleI7) (13.03 g) in water (200 ml) was added potassium carbonate (31.1 g).The reaction mixture was stirred at 95° C. for 1 hour. The reactionmixture was then allowed to cool to ambient temperature and was quenchedby addition of aqueous hydrochloric acid (5M) (250 ml). The mixture wasextracted with ethyl acetate (3×150 ml). The extracts were dried oversodium sulfate and concentrated. The residue was crystallized from ethylacetate and heptane to give 4-hydroxymethyl-2-trifluoromethyl-benzoicacid (9.07 g) as a white crystalline powder. ¹H-NMR (DMSO-d6, 400 MHz):13.5 (br s, 1H), 7.81-7.66 (m, 3H), 5.53 (s, 1H), 4.62 (s, 2H).

Similarly, 2-bromo-4-hydroxymethyl-benzoic acid was obtained from2-bromo-4-bromomethyl-benzoic acid (Example I7). ¹H-NMR (DMSO-d6, 400MHz): 13.36 (br s, 1H), 7.77-7.41 (m, 3H), 5.48 (s, 1H), 4.57 (s, 2H).

Example I9 Preparation of 4-hydroxymethyl-2-trifluoromethyl-benzoic acidmethyl ester

To a solution of 4-hydroxymethyl-2-trifluoromethyl-benzoic acid (ExampleI8) (9.07 g) in methanol (250 ml) was added toluene (250 ml) andconcentrated sulfuric acid (4.5 ml). The reaction mixture was stirred at80° C. for 16 hours. The methanol was removed and the residue dilutedwith aqueous sodium hydrogen carbonate (saturated) (150 ml) and ethylacetate (150 ml). The phases were separated and the aqueous layer wasextracted with more ethyl acetate (2×150 ml). The combined organicextracts were washed with brine, dried over sodium sulfate andconcentrated to give 4-hydroxymethyl-2-trifluoromethyl-benzoic acidmethyl ester (5.97 g) as a colorless oil. ¹H-NMR (CDCl₃, 400 MHz):8.76-7.27 (m, 3H), 4.78 (s, 2H), 3.93 (s, 3H), 2.5 (br s, 1H).

Similarly, 2-bromo-4-hydroxymethyl-benzoic acid methyl ester wasobtained from 2-bromo-4-hydroxymethyl-benzoic acid (Example I8). ¹H-NMR(CDCl₃, 400 MHz): 7.81-7.33 (m, 3H), 4.73 (s, 2H), 3.93 (s, 2.0 (br s,1H).

Example I10 Preparation of 4-formyl-2-trifluoromethyl-benzoic acidmethyl ester

To a solution of 4-hydroxymethyl-2-trifluoromethyl-benzoic acid methylester (Example I9) (7.15 g) in dichloromethane (150 ml) was addedmanganese dioxide (25.1 g). The reaction mixture stirred at ambienttemperature for 2.5 hours. The reaction mixture was filtered over a plugof silica gel and the filtrate concentrated to give4-formyl-2-trifluoromethyl-benzoic acid methyl ester (5.98 g), which wasused without further purification. ¹H-NMR (CDCl₃, 400 MHz): 10.11 (s,1H), 8.25-7.59 (m, 3H), 3.98 (s, 3H).

Similarly, 2-bromo-4-formyl-benzoic acid methyl ester was obtained from2-bromo-4-hydroxymethyl-benzoic acid methyl ester (Example I9). ¹H-NMR(CDCl₃, 400 MHz): 10.04 (s, 1H), 8.14-7.85 (m, 3H), 3.97 (s, 3H).

Example I11 Preparation of4-(hydroxyimino-methyl)-2-trifluoromethyl-benzoic acid methyl ester

To a suspension of 4-formyl-2-trifluoromethyl-benzoic acid methyl ester(Example I10) (5.98 g) and hydroxylamine hydrochloride (1.79 g) inmethanol (80 ml) was added triethylamine (5.4 ml). The reaction mixturewas stirred at ambient temperature for 1 hour. More hydroxylaminehydrochloride (5.4 g) was added and the reaction mixture was stirred atambient temperature for 16 hours. The solvent was removed and theresidue diluted with ethyl acetate (200 ml) and water (150 ml). Thephases were separated and the organic layer was washed with brine (100ml), dried over sodium sulfate and concentrated. The residue wasdissolved in a mixture of dichloromethane and heptane and crystallizedby slowly evaporating the dichloromethane to give4-(hydroxyimino-methyl)-2-trifluoromethyl-benzoic acid methyl ester(3.90 g) as a white crystalline powder. ¹H-NMR (CDCl₃, 400 MHz): 8.18(s, 1H), 7.97-7.64 (m, 4H), 3.95 (s, 3H).

Similarly, 2-bromo-4-(hydroxyimino-methyl)-benzoic acid methyl ester wasobtained from 2-bromo-4-formyl-benzoic acid methyl ester (Example I10).¹H-NMR (CDCl₃, 400 MHz): 8.08 (s, 1H), 7.89-7.54 (m, 4H), 3.95 (s, 3H).

Example I12 Preparation of4-(chloro(hydroxyimino)methyl)-2-trifluoromethyl-benzoic acid methylester

To a solution of 4-(hydroxyimino-methyl)-2-trifluoromethyl-benzoic acidmethyl ester (Example I11) (3.90 g) in N,N-dimethylformamide (20 ml) wasadded N-chlorosuccinimide (“NCS”) (2.318 g). The reaction mixture wasstirred at ambient temperature for 45 minutes. The reaction mixture waspoured into water (400 ml). The solids were isolated by filtration anddried to give 4-(chloro(hydroxyimino)methyl)-2-trifluoromethyl-benzoicacid methyl ester (4.21 g) as an off-white powder. ¹H-NMR (CDCl₃, 400MHz): 9.00 (s, 1H), 8.24-8.04 (m, 3H), 3.96 (s, 3H).

Similarly, 2-bromo-4-(chloro(hydroxyimino)methyl)-benzoic acid methylester was obtained from 2-bromo-4-(hydroxyimino-methyl)-benzoic acidmethyl ester (Example I11). ¹H-NMR (CDCl₃, 400 MHz): 8.92 (s, 1H),8.16-7.83 (m, 3H), 3.96 (s, 3H).

Example I13 Preparation of4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-trifluoromethyl-benzoicacid methyl ester

To a solution of4-(chloro(hydroxyimino)methyl)-2-trifluoromethyl-benzoic acid methylester (Example I12) (4.21 g) in isopropanol (100 ml) was addedsequentially sodium hydrogen carbonate (2.90 g) and1,3-dichloro-5-(1-trifluoromethyl-vinyl)-benzene (4.22 g) (preparedaccording to WO 2005/085216). The reaction mixture was stirred at 60° C.for 16 hours. The isopropanol was removed by distillation. The residuewas purified over silica gel (eluent: ethyl acetate/heptane gradientfrom 0:1 to 2:3) to give4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-trifluoromethyl-benzoicacid methyl ester (4.30 g). ¹H-NMR (CDCl₃, 400 MHz): 8.00-7.44 (m, 6H),4.12 (d, 1H), 3.96 (s, 3H), 3.74 (d, 1H).

Similarly,2-bromo-4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzoicacid methyl ester was obtained from2-bromo-4-(chloro(hydroxy-imino)methyl)-benzoic acid methyl ester(Example I12). ¹H-NMR (CDCl₃, 400 MHz): 7.92-7.43 (m, 6H), 4.08 (d, 1H),3.95 (s, 3H), 3.70 (d, 1H).

Example I14 Preparation of2-cyano-4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzoicacid methyl ester

To a solution of2-bromo-4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzoicacid methyl ester (Example I13) (2.52 g) in dry N,N-dimethylformamide(75 ml) was added copper(I) cyanide (1.145 g). The reaction mixture wasstirred at 160° C. for 40 minutes. The reaction mixture was allowed tocool to ambient temperature and was poured into a mixture of aqueoussodium carbonate (saturated) and water (1:2) (150 ml). The mixture wasextracted with ethyl acetate (3×70 ml). The combined organic extractswere washed with water (2×70 ml) and brine (70 ml), dried over sodiumsulfate and concentrated. The residue was re-crystallized from a mixtureof diethyl ether and heptane (1:1) to give methyl2-cyano-4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzoicacid methyl ester (1.474 g). ¹H-NMR (CDCl₃, 400 MHz): 8.23-7.45 (m, 6H),4.11 (d, 1H), 4.03 (s, 3H), 3.74 (d, 1H).

Example I15 Preparation of4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-trifluoromethyl-benzoicacid

To a solution of4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-trifluoromethyl-benzoicacid methyl ester (Example I13) (4.3 g) in tetrahydrofuran (3 ml) andmethanol (3 ml) was added a solution of potassium hydroxide (1.0 g) inwater (4.0 ml). The reaction mixture was stirred at ambient temperaturefor 2 hours. The reaction mixture was acidified by addition ofhydrochloric acid (2M) (200 ml) and the mixture extracted with ethylacetate (3×100 ml). The combined organic extracts were washed withbrine, dried over sodium sulfate and concentrated. The residue wasre-crystallized from dichloromethane and heptane to give4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-trifluoromethyl-benzoicacid (3.58 g) as a white powder. ¹H-NMR (CDCl₃, 400 MHz): 8.08-7.45 (m,6H), 4.14 (d, 1H), 3.76 (d, 1H).

Similarly,2-bromo-4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzoicacid was obtained from2-bromo-4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzoicacid methyl ester (Example I13). ¹H-NMR (DMSO-d6, 400 MHz): 13.74 (br s,1H), 8.00-7.62 (m, 6H), 4.41 (m, 2H).

Similarly,2-cyano-4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzoicacid was obtained from2-cyano-4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzoicacid methyl ester (Example I14). ¹H-NMR (DMSO-d6, 400 MHz): 14.15 (br s,1H), 8.24-7.62 (m, 6H), 4.52 (d, 1H), 4.42 (d, 1H).

Example I16 Preparation of 4-bromo-2-methyl-benzoic acid tert-butylester

4-Bromo-2-methyl-benzoic acid (commercially available) (50 g) wassuspended in dichloromethane (500 ml). A catalytic amount ofN,N-dimethylformamide (“DMF”) and oxalyl chloride (23 ml) were added tothe suspension. The reaction mixture was stirred at ambient temperaturefor 3 hours. The reaction mixture was concentrated and the residuedissolved in dry tetrahydrofuran (800 ml). The solution was cooled to 2°C. and added to a solution of potassium tert-butoxide (39.2 g) in drytetrahydrofuran (300 ml) dropwise at 5-10° C. The reaction mixture wasstirred at ambient temperature for 30 minutes and then poured onto amixture of ice and water. The mixture was extracted with ethyl acetate.The organic extract was washed with water, dried over sodium sulfate andconcentrated to give 4-bromo-2-methyl-benzoic acid tert-butyl ester(65.3 g) as a yellow oil, which was used without further purification.¹H-NMR (CDCl₃, 400 MHz): 7.70 (d, 1H), 7.40 (s, 1H), 7.35 (d, 1H), 2.58(s, 3H), 1.60 (s, 9H).

Example I17 Preparation of 4-formyl-2-methyl-benzoic acid tert-butylester

A solution of 4-bromo-2-methyl-benzoic acid tert-butyl ester (ExampleI16) (75 g) in dry tetrahydrofuran (750 ml) was cooled to −100° C. Asolution of n-butyl lithium (1.6 M in hexane) (163 ml) was addeddropwise at −100° C. The reaction mixture was stirred at −95° C. for 20minutes. N,N-Dimethylformamide (43 ml) was added dropwise. The reactionmixture was stirred at −95° C. for 45 minutes. The reaction was quenchedby addition of aqueous ammonium chloride (saturated) (8 ml) at −90° C.The mixture was stirred for 10 minutes at −90° C., warmed to 0° andpoured on a mixture of ice and water. The mixture was allowed to warm toambient temperature and then extracted twice with ethyl acetate. Thecombined organic phases were washed with water, dried over sodiumsulfate, and concentrated to give 4-formyl-2-methyl-benzoic acidtert-butyl ester (60.3 g) as yellow oil. ¹H-NMR (CDCl₃, 400 MHz): 10.03(s, 1H), 7.93 (d, 1H), 7.75 (m, 2H), 2.65 (s, 3H), 1.65 (s, 9H).

Example I18 Preparation of 4-(hydroxyimino-methyl)-2-methyl-benzoic acidtert-butyl ester

To a suspension of 4-formyl-2-methyl-benzoic acid tert-butyl ester(Example I17) (60.3 g) and hydroxylamine hydrochloride (38.05 g) inethanol (580 ml) was added a solution of sodium hydrogen carbonate (46g) in water (60 ml). The reaction mixture was stirred at 50° C. for 3.5hours. The solvent was removed and the residue diluted with ethylacetate and water. The phases were separated and the organic layer waswashed with water, dried over sodium sulfate and concentrated. Theresidue was crystallized from ethyl acetate and heptane to give4-(hydroxyimino-methyl)-2-methyl-benzoic acid tert-butyl ester (35.72 g)as a white crystalline powder. ¹H-NMR (CDCl₃, 400 MHz): 7.86 (s, 1H),7.70 (s, 1H), 7.45 (m, 2H), 2.60 (s, 3H), 1.60 (s, 9H).

Example I19 Preparation of4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid tert-butyl ester

To a solution of 4-(hydroxyimino-methyl)-2-methyl-benzoic acidtert-butyl ester (Example I18) (32.5 g) in N,N-dimethylformamide (280ml) was added N-chlorosuccinimide (“NCS”) (18.44 g). The reactionmixture was stirred at ambient temperature for 3.5 hour. A solution of1,3-dichloro-5-(1-trifluoromethyl-vinyl)-benzene (33.3 g) (preparedaccording to WO 2005/085216) and triethylamine (19.25 ml) inN,N-dimethylformamide (220 ml) was added dropwise to the reactionmixture. The reaction mixture was stirred at ambient temperature for 16hours. Water and ethyl acetate were added and the phases were separated.The organic layer was washed with water, dried over sodium sulfate andconcentrated. The residue was crystallized from ethyl acetate andheptane to give4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid tert-butyl ester (40.12 g). ¹H-NMR (CDCl₃, 400 MHz): 7.88 (d, 1H),7.55-7.45 (m, 5H), 4.10 (d, 1H), 3.75 (d, 1H), 2.60 (s, 3H), 1.65 (s,9H).

Similarly,2-methyl-4-[5-trifluoromethyl-5-(3-trifluoromethyl-phenyl)-4,5-dihydro-isoxazol-3-yl]-benzoicacid tert-butyl ester was obtained when1-trifluoromethyl-3-(1-trifluoromethyl-vinyl)-benzene (preparedaccording to WO 2005/085216) was used as reagent. ¹H-NMR (CDCl₃, 400MHz): 7.87-7.26 (m, 7H), 4.14 (d, 1H), 3.75 (d, 1H), 2.59 (s, 3H), 1.60(s, 9H).

Similarly,4-[5-(3,5-bis-trifluoromethyl-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid tert-butyl ester was obtained when1,3-bis-trifluoromethyl-5-(1-trifluoromethyl-vinyl)-benzene (preparedaccording to WO 2005/085216) was used as reagent. ¹H-NMR (CDCl₃, 400MHz): 8.09-7.52 (m, 6H), 4.21 (d, 1H), 3.76 (d, 1H), 2.59 (s, 3H), 1.60(s, 9H).

Example I20 Alternative preparation of4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid

To a solution of4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid tert-butyl ester (Example I19) (74.14 g) in dichloromethane (750ml) was added trifluoromethyl acetic acid (“TFA”) (148 ml). The reactionmixture was stirred at ambient temperature for 16 hours. Ethyl acetatewas added and the mixture was washed with water, dried over sodiumsulfate and concentrated. The residue was crystallized from ethylacetate and heptane to give4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid (55.0 g). ¹H-NMR (CDCl₃, 400 MHz): 8.12 (d, 1H), 7.65-7.45 (m, 5H),4.15 (d, 1H), 3.75 (d, 1H), 2.75 (s, 3H).

Similarly,4-[5-(3-trifluoromethyl-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid was obtained when4-[5-(3-trifluoromethyl-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid tert-butyl ester (Example I19) was used as starting material.¹H-NMR (DMSO-d6, 400 MHz): 13.16 (s, 1H), 7.96-7.67 (m, 7H), 4.49 (d,1H), 4.32 (d, 1H), 2.57 (s, 3H).

Similarly,4-[5-(3,5-bis-trifluoromethyl-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid was obtained when4-[5-(3,5-bis-trifluoromethyl-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid tert-butyl ester (Example I19) was used as starting material.¹H-NMR (DMSO-d6, 400 MHz): 13.18 (s, 1H), 8.35-7.67 (m, 6H), 4.50 (m,2H), 2.58 (s, 3H).

Example I21 Preparation of4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-iodo-6-methyl-benzoicacid

A sealed tube purged with argon was charged with4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid (Example I5) (836 mg), palladium(II) acetate (45 mg), phenyliododiacetate (1.28 g) and iodine (508 mg). N,N-Dimethylformamide (10ml) was added and the reaction mixture was stirred at 100° C. for 1hour. The reaction mixture was cooled to ambient temperature then pouredinto water. The mixture was extracted three times with ethyl acetate (25ml). The combined organic extracts were washed with water and brine,then dried over sodium sulfate and concentrated. The residue waspurified by chromatography on silica gel (eluent:dichloromethane/methanol) to afford4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-iodo-6-methyl-benzoicacid (700 mg) as a yellow solid. ¹H-NMR (CDCl₃, 400 MHz): 7.20-7.80 (m,6H), 4.05 (d, 1H), 3.70 (d, 1H), 2.25 (s, 3H).

Similarly,4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-bromo-6-methyl-benzoicacid was obtained when tetrabutylammonium bromide was used in additionto palladium(II) acetate, phenyl iododiacetate and iodine. ¹H-NMR(CDCl₃, 400 MHz): 7.65 (s, 1H), 7.40 (m, 3H), 7.35 (s, 1H), 4.00 (d,1H), 3.60 (d, 1H), 2.40 (s, 3H).

Example I22 Preparation of5-bromo-4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid methyl ester

A sealed tube purged with argon was charged with4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid methyl ester (Example I6) (432 mg), palladium(II) acetate (23 mg)and N-bromosuccinimide (“NBS”) (356 mg). Acetic acid (10 ml) was addedand the reaction mixture was stirred at 100° C. for 96 hours. Thereaction mixture was cooled to ambient temperature then poured intowater. The mixture was extracted three times with ethyl acetate (25 ml).The combined organic extracts were washed with water and brine, driedover sodium sulfate and concentrated. The residue was purified bychromatography on silica gel (eluent: cyclohexane/ethyl acetate) toafford5-bromo-4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid methyl ester (150 mg) as a colorless resin. ¹H-NMR (CDCl₃, 400MHz): 8.10 (s, 1H), 7.30-7.50 (m, 4H), 4.20 (d, 1H), 3.80 (s, 3H), 3.75(d, 1H), 2.45 (s, 3H).

Similarly,5-chloro-4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid methyl ester was obtained N-chlorosuccinimide (“NCS”) was usedinstead of N-bromosuccinimide. ¹H-NMR (CDCl₃, 400 MHz): 7.90 (s, 1H),7.50 (s, 1H), 7.40 (s, 2H), 7.35 (s, 1H), 4.20 (d, 1H), 3.80 (s, 3H),3.75 (d, 1H), 2.50 (s, 3H).

Example I23 Preparation of5-bromo-4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid

To a solution of5-bromo-4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid methyl ester (Example I22) (290 mg) in tetrahydrofuran (3 ml) wasadded a solution of potassium hydroxide (1.53 g) in methanol (3 ml) andwater (3 ml). The reaction mixture was stirred at ambient temperaturefor 2 hours. The reaction mixture was acidified by addition of aqueoushydrochloric acid (4N). The aqueous phase was extracted with ethylacetate (3×10 ml). The combined organic extracts were washed with water(3×10 ml) and brine, dried over sodium sulfate, and concentrated toafford5-bromo-4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid (220 mg) as a white foam. ¹H-NMR (CDCl₃, 400 MHz): 8.20 (s, 1H),7.30-7.50 (m, 4H), 4.20 (d, 1H), 3.80 (d, 1H), 2.50 (s, 3H).

Similarly,5-chloro-4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid was obtained from5-chloro-4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid methyl ester (Example I22). ¹H-NMR (CDCl₃, 400 MHz): 8.05 (s, 1H),7.55 (s, 1H), 7.42 (s, 2H), 7.38 (s, 1H), 4.20 (d, 1H), 3.80 (d, 1H),2.55 (s, 3H).

Example P1 Preparation of4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-N-(3-methyl-thietan-3-yl)-benzamide(Compound No. A1 of Table A)

To a solution of4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid (0.5 g) (Example I5) in dichloromethane (3 ml) was added oxalylchloride (0.122 ml). After addition of N,N-dimethylformamide (“DMF”) (2drops) the reaction mixture was stirred at ambient temperature for 18hours. The reaction mixture was concentrated to give the acid chlorideas a yellow solid, which was used without further purification.Triethylamine (0.05 ml) and 3-methyl-thietan-3-ylamine (28 mg) (preparedaccording to WO 2007/080131) were added to a solution of the acidchloride (100 mg) in toluene (4 ml). The reaction mixture was stirred atambient temperature for 2 hours. The reaction mixture was diluted withwater and ethyl acetate and the phases were separated. The organic phasewas washed twice with water, dried over sodium sulfate and concentrated.The residue was purified by preparative HPLC to give Compound No. A1 ofTable A (118 mg) as a colorless solid. ¹H-NMR (CDCl₃, 400 MHz):7.55-7.45 (m, 6H), 5.90 (s, 1H), 4.05 (d, 1H), 3.85 (d, 2H), 3.70 (d,1H), 3.10 (d, 2H), 2.50 (s, 3H), 1.85 (s, 3H) ppm.

Similarly, 2,2-dimethyl-thietan-3-ylamine (prepared according to WO2007/080131), 2,2,4,4-tetramethyl-thietan-3-ylamine (prepared accordingto WO 2007/080131), thietan-3-ylamine (prepared according to WO2007/080131), 3-(aminomethyl)-azetidine-1-carboxylic acid tert-butylester (CAS RN 325775-44-8, commercially available), and1-(benzyl)-2-azetidinemethanamine (CAS RN 46193-94-6, commerciallyavailable) were used instead of 3-methyl-thietan-3-ylamine to obtainCompound Nos. A2, A3 and A4 of Table A, and Compound Nos. B1 and B2 ofTable B, respectively.

Similarly,4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]-2-trifluoromethyl-benzoicacid (Example I14),2-bromo-4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzoicacid (Example I14), and2-cyano-4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzoicacid (Example I14) were used instead of4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid to obtain Compound Nos. A14-A19 of Table A, respectively.

Similarly,4-[5-(3-trifluoromethyl-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid (Example I19) and4-[5-(3,5-bis-trifluoromethyl-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid (Example I19) were used instead of4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid to obtain Compound Nos. A20, A21, A23, and A24 of Table A,respectively.

Similarly,4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-bromo-6-methyl-benzoicacid (Example I20),4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-iodo-6-methyl-benzoicacid (Example I20),5-bromo-4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid (Example I22) and5-chloro-4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid (Example I22) were used instead of4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoicacid to obtain Compound Nos. C1-C4 of Table C, respectively.

Example P2 Preparation of4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-N-(3-methyl-1-oxo-thietan-3-yl)-benzamide(Compounds No. A6 and A7 of Table A) and4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-N-(3-methyl-1,1-dioxo-thietan-3-yl)-benzamide(Compound No. A5 of Table A)

To a solution of4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-N-(3-methyl-thietan-3-yl)-benzamide(Example P1) (81 mg) in dichloromethane (6 ml) was added a solution ofsodium hydrogen carbonate (81 mg) in water (2 ml). A solution of3-chloroperbenzoic acid (“MCPBA”) (40 mg) in dichloromethane (1 ml) wasadded dropwise at 0° C. The reaction mixture was stirred at 0° C. for 30minutes and at ambient temperature for 3 hours. The reaction mixture wasextracted twice with dichloro-methane. The combined organic phases werewashed with brine, dried over sodium sulfate and concentrated. Theresidue was purified by preparative HPLC to give Compound No. A6 ofTable A (48 mg), Compound No. A7 of Table A (12 mg) and Compound No. A5of Table A (16 mg), all as colorless solids.

Compound No. A6 of Table A. ¹H-NMR (CDCl₃, 400 MHz): 7.55-7.35 (m, 6H),6.05 (s, 1H), 4.10 (d, 1H), 3.95 (d, 2H), 3.65 (d, 2H), 3.60 (d, 2H),2.45 (s, 3H), 1.60 (s, 3H) ppm.

Compound No. A7 of Table A. ¹H-NMR (CDCl₃, 400 MHz): 7.55-7.45 (m, 6H),6.00 (s, 1H), 4.25 (d, 2H), 4.05 (d, 1H), 3.65 (d, 111), 3.25 (d, 2H),2.45 (s, 3H), 1.80 (s, 3H) ppm.

Compound No. A5 of Table A. ¹H-NMR (CDCl₃, 400 MHz): 7.55-7.45 (m, 6H),6.20 (s, 1H), 4.50 (d, 2H), 4.20 (d, 1H), 4.05 (d, 2H), 3.70 (d, 1H),2.45 (s, 3H), 1.90 (s, 3H) ppm.

The following compounds were made using the same method: Compound Nos.A8-A10, A11-A12, A22 and A25 of Table A.

Example P3 Preparation of4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-N-(1-oxo-1-(2,2,2-trifluoro-acetylimino)-thietan-3-yl)-benzamide

To a solution of4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-N-(1-oxo-thietan-3-yl)-benzamide(Example P2) (0.2 g) in dichloromethane (20 ml) was addedtrifluoroacetamide (0.09 g), rhodium(II) acetate dimer (0.02 g),magnesium oxide (0.07 g) and iodobenzene diacetate (0.19 g). Thereaction mixture was stirred at ambient temperature for 42 hours. Thereaction mixture was concentrated and the residue purified bychromatography on silica gel (eluent: ethyl acetate/heptane 1:1) to give4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-N-[1-oxo-1-(2,2,2-trifluoro-acetylimino)-thietan-3-yl]-benzamide(0.06 g) as an off-white powder. HPLC-MS: RT 2.14 min and 2.18 min (twoisomers) MH+ 616.

Example P4 Preparation of4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-N-(1-imino-1-oxo-thietan-3-yl)-2-methyl-benzamide(Compound No. A13 of Table A)

To a solution of4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-N-[1-oxo-1-(2,2,2-trifluoro-acetylimino)-thietan-3-yl]-benzamide(Example P3) (0.05 g) in methanol (5 ml) was added potassium carbonate(0.06 g). The reaction mixture was stirred at ambient temperature for 4hours. Water (0.5 ml) was added and the reaction mixture wasconcentrated and the residue purified by chromatography on silica gel(eluent: dichloromethane/methanol 9:1) to give Compound No. A13 of TableA (0.02 g) as an amorphous solid. ¹H-NMR (CDCl₃, 400 MHz): 7.85 (d, 1H),7.45-7.55 (m, 6H), 6.95 (d, 1H), 4.1-4.9 (m, 6H), 4.05 (d, 1H), 3.7 (d,1H), 2.9-3.2 (m, 2H), 2.45 (s, 3H) ppm.

The following method was used for HPLC-MS analysis:

Method (Agilent 1100 LC) with the following HPLC gradient conditions(Solvent A: 0.05% of formic acid in water and Solvent B: 0.04% of formicacid in acetonitrile/methanol 4:1)

Time Flow rate (minutes) A (%) B (%) (ml/min) 0 95 5 1.7 2.0 0 100 1.72.8 0 100 1.7 2.9 95 5 1.7 3.1 95 5 1.7Type of column: Phenomenex Gemini C18; Column length: 30 mm; Internaldiameter of column: 3 mm; Particle Size: 3 micron; Temperature: 60° C.

The characteristic values obtained for each compound were the retentiontime (“RT”, recorded in minutes) and the molecular ion, typically thecation MH⁺ as listed in Table A, Table B and Table C.

TABLE A Compounds of formula (Ia): (Ia)

Comp RT No. R³ R⁴ R⁵ R² Y¹ Y² Y³ (min) MH⁺ Al —CF₃ 3,5-dichloro-phenyl-Me Me CH₂ S CH₂ 2.24 503 A2 —CF₃ 3,5-dichloro-phenyl- Me H C(Me)₂ S CH₂2.28 517 A3 —CF₃ 3,5-dichloro-phenyl- Me H C(Me)₂ S C(Me)₂ 2.35 545 A4—CF₃ 3,5-dichloro-phenyl- Me H CH₂ S CH₂ 2.19 489 A5 —CF₃3,5-dichloro-phenyl- Me Me CH₂ SO₂ CH₂ 2.11 535 A6 —CF₃3,5-dichloro-phenyl- Me Me CH₂ SO* CH₂ 2.05 519 A7 —CF₃3,5-dichloro-phenyl- Me Me CH₂ SO** CH₂ 2.05 519 A8 —CF₃3,5-dichloro-phenyl- Me H CH₂ SO* CH₂ 2.01 505 A9 —CF₃3,5-dichloro-phenyl- Me H CH₂ SO** CH₂ 2.01 505 A10 —CF₃3,5-dichloro-phenyl- Me H CH₂ SO₂ CH₂ 2.07 521 A11 —CF₃3,5-dichloro-phenyl- Me H C(Me)₂ SO* CH₂ 2.05 533 A12 —CF₃3,5-dichloro-phenyl- Me H C(Me)₂ SO** CH₂ 2.03 533 A13 —CF₃3,5-dichloro-phenyl- Me H CH₂ SONH CH₂ 1.95 520 A14 —CF₃3,5-dichloro-phenyl- —CF₃ Me CH₂ S CH₂ 2.16 557 A15 —CF₃3,5-dichloro-phenyl- —CF₃ H CH₂ S CH₂ 2.08 543 A16 —CF₃3,5-dichloro-phenyl- —Br Me CH₂ S CH₂ 2.22 569 A17 —CF₃3,5-dichloro-phenyl- —Br H CH₂ S CH₂ 2.10 555 A18 —CF₃3,5-dichloro-phenyl- —CN Me CH₂ S CH₂ 2.13 514 A19 —CF₃3,5-dichloro-phenyl- —CN H CH₂ S CH₂ 1.85 498 A20 —CF₃3-trifluoromethyl-phenyl- Me H CH₂ S CH₂ 1.89 489 A21 —CF₃3,5-bis-(trifluoromethyl)-phenyl- Me Me CH₂ S CH₂ 2.16 571 A22 —CF₃3,5-bis-(trifluoromethyl)-phenyl- Me H CH₂ SO^(#) CH₂ 1.72 573 A23 —CF₃3,5-bis-(trifluoromethyl)-phenyl- Me H CH₂ S CH₂ 2.06 557 A24 —CF₃3-trifluoromethyl-phenyl- Me Me CH₂ S CH₂ 1.98 503 A25 —CF₃3-trifluoromethyl-phenyl- Me H CH₂ SO^(#) CH₂ 1.53 505 ^(#)= Mixture ofdiastereomer A and diastereomer B; *= Diastereomer A (absolutestereochemistry unknown); **= Diastereomer B (absolute stereochemistryunknown).

TABLE B Compounds of formula (Ib): (Ib)

Comp No. R⁵ R² Y¹ Y² Y³ RT (min) MH⁺ B1 Me H CH₂ N—CO—OC(CH₃)₃ CH₂ 2.21586 B2 Me H N—CH₂—C₆H₅ CH₂ CH₂ 1.54 576

TABLE C Compounds of formula (Ic): (Ic)

Comp RT No. R³ R⁴ R^(5a) R^(5b) R^(5c) R^(5d) M.p. (min) MH⁺ C1 —CF₃3,5- Me H H Br 107° C. 2.20 567/ dichloro- 569 phenyl- C2 —CF₃ 3,5- Me HH I  87° C. 2.24 615/ dichloro- 616 phenyl- C3 —CF₃ 3,5- Me H Br H  92°C. 2.22 567/ dichloro- 569 phenyl- C4 —CF₃ 3,5- Me H Cl H  63.5 2.22521/ dichloro- 522 phenyl-

BIOLOGICAL EXAMPLES

This Example illustrates the pesticidal/insecticidal properties ofcompounds of formula (I). Tests were performed as follows:

Spodoptera littoralis (Egyptian Cotton Leafworm):

Cotton leaf discs were placed on agar in a 24-well microtiter plate andsprayed with test solutions at an application rate of 200 ppm. Afterdrying, the leaf discs were infested with 5 L1 larvae. The samples werechecked for mortality, feeding behavior, and growth regulation 3 daysafter treatment (DAT).

The following compounds gave at least 80% control of Spodopteralittoralis: A1, A2, A3, A4, A5, A6, A7, A8, A9, A10, A11, A12, A13, A14,A15, A16, A17, A20, A21, A22, A23, A24, A25.

Heliothis virescens (Tobacco Budworm):

Eggs (0-24 h old) were placed in 24-well microtiter plate on artificialdiet and treated with test solutions at an application rate of 200 ppm(concentration in well 18 ppm) by pipetting. After an incubation periodof 4 days, samples were checked for egg mortality, larval mortality, andgrowth regulation.

The following compounds gave at least 80% control of Heliothisvirescens: A1, A2, A3, A4, A5, A6, A7, A8, A9, A10, A11, A12, A13, A14,A15, A16, A17, A20, A21, A22, A23, A24, A25, C1, C2, C3, C4.

Plutella xylostella (Diamond Back Moth):

24-well microtiter plate (MTP) with artificial diet was treated withtest solutions at an application rate of 200 ppm (concentration in well18 ppm) by pipetting. After drying, the MTP's were infested with L2larvae (7-12 per well). After an incubation period of 6 days, sampleswere checked for larval mortality and growth regulation.

The following compounds gave at least 80% control of Plutellaxylostella: A1, A2, A3, A4, A5, A6, A7, A8, A9, A10, A11, A12, A13, A14,A15, A16, A17, A20, A21, A22, A23, A24, A25, C1, C2, C3, C4.

Diabrotica balteata (Corn Root Worm):

A 24-well microtiter plate (MTP) with artificial diet was treated withtest solutions at an application rate of 200 ppm (concentration in well18 ppm) by pipetting. After drying, the MTP's were infested with L2larvae (6-10 per well). After an incubation period of 5 days, sampleswere checked for larval mortality and growth regulation.

The following compounds gave at least 80% control of Diabroticabalteata: A1, A2, A3, A4, A5, A6, A7, A8, A9, A10, A11, A12, A13, A14,A15, A16, A17, A20, A21, A22, A23, A24, A25, B1, C1, C2, C3, C4.

Thrips tabaci (Onion Trips):

Sunflower leaf discs were placed on agar in a 24-well microtiter plateand sprayed with test solutions at an application rate of 200 ppm. Afterdrying, the leaf discs were infested with an aphid population of mixedages. After an incubation period of 7 days, samples were checked formortality.

The following compounds gave at least 80% control of Thrips tabaci: A1,A2, A3, A4, A5, A6, A7, A8, A9, A10, A11, A12, A13, A14, A15, A16, A17,A20, A21, A22, A23, A24, A25, C2, C3, C4.

Tetranychus urticae (Two-Spotted Spider Mite):

Bean leaf discs on agar in 24-well microtiter plates were sprayed withtest solutions at an application rate of 200 ppm. After drying, the leafdiscs are infested with mite populations of mixed ages. 8 days later,discs are checked for egg mortality, larval mortality, and adultmortality.

The following compounds gave at least 80% control of Tetranychusurticae: A1, A2, A3, A4, A5, A6, A7, A8, A9, A10, A11, A12, A13, A14,A15, A16, A17, A20, A21, A22, A23, A24, A25.

Compound Nos. A18 and A19, and Compound No. B2 of Table B was testedusing the same protocols and showed little or no effect on mortality,feeding behavior, or growth regulation under the test conditions.

The invention claimed is:
 1. A compound of formula (I)

wherein A¹, A², A³ and A⁴ are independently of one another C—H, C—R⁵, ornitrogen; G¹ is oxygen or sulfur; L is a single bond, C₁-C₈alkyl,C₁-C₈haloalkyl, C₂-C₈alkenyl, C₂-C₈haloalkenyl, C₂-C₈alkynyl, orC₂-C₈haloalkynyl; R¹ is hydrogen, C₁-C₈alkyl, C₁-C₈alkylcarbonyl-, orC₁-C₈alkoxycarbonyl-; R² is hydrogen, or C₁-C₈alkyl; R³ isC₁-C₈haloalkyl; R⁴ is aryl or aryl substituted by one to three R⁶, orheterocyclyl or heterocyclyl substituted by one to three R⁶; Y¹, Y² andY³ are independently of another CR⁷R⁸, S, SO, SO₂, provided that atleast one of Y¹, Y² or Y³ is not CR⁷R⁸; each R⁵ is independentlyhalogen, cyano, nitro, C₁-C₈alkyl, C₁-C₈haloalkyl, C₂-C₈alkenyl,C₂-C₈haloalkenyl, C₂-C₈alkynyl, C₂-C₈haloalkynyl, C₁-C₈alkoxy,C₁-C₈haloalkoxy, C₁-C₈alkoxycarbonyl-, aryl or aryl optionallysubstituted by one to three R¹⁰, or heteroaryl or heteroaryl optionallysubstituted by one to three R¹⁰, or where two R⁵ are adjacent, the twoR⁵ may together with the carbon atoms to which the two R⁵ are bondedform a 5-membered ring, wherein the 5-membered ring is —OCH═N—, —SCH═N—,—OCR¹⁰═N—, or —SCR¹⁰═N—; each R⁶ is independently halogen, cyano, nitro,C₁-C₈alkyl, C₁-C₈haloalkyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy, orC₁-C₈alkoxycarbonyl-; each R⁷ and R⁸ is independently hydrogen, halogen,C₁-C₈alkyl, or C₁-C₈haloalkyl; each R¹⁰ is independently halogen, cyano,nitro, C₁-C₈alkyl, C₁-C₈haloalkyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy, orC₁-C₈alkoxycarbonyl-; and; or a salt or N-oxide thereof; wherein theterm “aryl” refers to phenyl, naphthalenyl, anthracenyl, indenyl orphenanthrenyl; wherein the term “heterocyclyl” refers to heteroaryl andtheir unsaturated or partially unsaturated analogues; and wherein theterm “heteroaryl” refers to a monocyclic group selected from pyridyl,pyridazinyl, pyrimidinyl, pyrazinyl, pyrrolyl, pyrazolyl, imidazolyl,triazolyl, tetrazolyl, furanyl, thiophenyl, oxazolyl, isoxazolyl,oxadiazolyl, thiazolyl, isothiazolyl, and thiadiazolyl, or a bicyclicgroup selected from quinolinyl, cinnolinyl, quinoxalinyl,benzimidazolyl, benzothiophenyl, and benzothiadiazolyl.
 2. A compoundaccording to claim 1 wherein A¹ is C—R⁵; A² is C—H; A³ is C—H; and A⁴ isC—H and wherein G¹ is oxygen.
 3. A compound according to claim 1 whereinL is a single bond, C₁-C₈alkyl, or C₁-C₈haloalkyl.
 4. A compoundaccording to claim 1 wherein R¹ is hydrogen, methyl, ethyl,methylcarbonyl-, or methoxycarbonyl-.
 5. A compound according to claim 1wherein R² is hydrogen or methyl.
 6. A compound according to claim 1wherein R³ is chlorodifluoromethyl or trifluoromethyl.
 7. A compoundaccording to claim 1 wherein R⁴ is phenyl or phenyl substituted by oneto three R⁶.
 8. A compound according to claim 1 wherein Y² is S, SO, orSO₂, and Y¹ and Y³ are independently of another CR⁷R⁸.
 9. A compoundaccording to claim 1 wherein each R⁵ is independently halogen, cyano,nitro, C₁-C₈alkyl, C₁-C₈haloalkyl, C₂-C₈alkenyl, C₂-C₈haloalkenyl,C₂-C₈alkynyl, C₂-C₈haloalkynyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy, orC₁-C₈alkoxycarbonyl-.
 10. A compound according to claim 1 wherein eachR⁷ and R⁸ is independently hydrogen or methyl.
 11. A compound of formula(XI)

wherein A¹, A², A³, A⁴, G¹, L, R¹, R², Y¹, Y² and Y³ are as defined inclaim 1; or a salt or N-oxide thereof; or a compound of formula (XI′)

wherein A¹, A², A³, A⁴, G¹, L, R¹, R², Y¹, Y² and Y³ are as defined inclaim 1; or a salt or N-oxide thereof; or a compound of formula (XII)

wherein A¹, A², A³, A⁴, G¹, L, R¹, R², Y¹, Y² and Y³ are as defined inclaim 1; or a salt or N-oxide thereof; or a compound of formula (XIII)

wherein A¹, A², A³, A⁴, G¹, L, R¹, R², Y¹, Y² and Y³ are as defined inclaim 1 and X^(B) is halogen; or a salt or N-oxide thereof; or acompound of formula (XIV)

wherein A¹, A², A³, A⁴, G¹, L, R¹, R², Y¹, Y² and Y³ are as defined inclaim 1; or a salt or N-oxide thereof; or a compound of formula (XV)

wherein A¹, A², A³, A⁴, G¹, L, R¹, R², Y¹, Y² and Y³ are as defined inclaim 1; or a salt or N-oxide thereof; or a compound of formula (XVIII)

wherein A¹, A², A³, A⁴, G¹, L, R¹, R², Y¹, Y² and Y³ are as defined inclaim 1; or a salt or N-oxide thereof; or a compound of formula (XIX)

wherein A¹, A², A³, A⁴, G¹, L, R¹, R², R³, R⁴, Y¹, Y² and Y³ are asdefined in claim 1; or a salt or N-oxide thereof; or a compound offormula (XX)

wherein A¹, A², A³, A⁴, G¹, L, R¹, R², R³, R⁴, Y¹, Y² and Y³ are asdefined in claim 1; or a salt or N-oxide thereof; or a compound offormula (XXII)

wherein A¹, A², A³, A⁴, G¹, L, R¹, R², Y¹, Y² and Y³ are as defined inclaim 1; or a salt or N-oxide thereof; or a compound of formula (XXIII)

wherein A¹, A², A³, A⁴, G¹, L, R¹, R², Y¹, Y² and Y³ are as defined inclaim 1 and Hal is a halogen; or a salt or N-oxide thereof; or acompound of formula (XXIV)

wherein A¹, A², A³, A⁴, G¹, L, R¹, R², R³, R⁴, Y¹, Y² and Y³ are asdefined in claim 1; or a salt or N-oxide thereof; or a compound offormula (XXIV′)

wherein A¹, A², A³, A⁴, G¹, L, R¹, R², R³, R⁴, Y¹, Y² and Y³ are asdefined in claim 1; or a salt or N-oxide thereof.
 12. A method ofcombating and controlling insects, acarines, nematodes or molluscs whichcomprises applying to a pest, to a locus of a pest, or to a plantsusceptible to attack by a pest an insecticidally, acaricidally,nematicidally or molluscicidally effective amount of a compound offormula (I) as defined in claim
 1. 13. An insecticidal, acaricidal,nematicidal or molluscicidal composition comprising an insecticidally,acaricidally, nematicidally or molluscicidally effective amount of acompound of formula (I) as defined in claim 1, and which can furthercomprise another compound having biological activity.
 14. A compoundaccording to claim 1 or claim 2 wherein L is a single bond or CH₂.
 15. Acompound according to claim 1 wherein R⁴ is phenyl substituted by one tothree R⁶.
 16. A compound according to claim 1 wherein each R⁵ isindependently chloro, fluoro or methyl.
 17. A compound according toclaim 1 wherein each R⁶ is independently bromo, chloro, fluoro, cyano,nitro, methyl, ethyl, trifluoromethyl, methoxy, difluoromethoxy,trifluoromethoxy, or methoxycarbonyl.
 18. A compound according to claim1 wherein each R⁶ is independently bromo, chloro or fluoro.
 19. Acompound according to claim 1 wherein A¹ is C—R⁵; A² is C—H; A³ is C—H;and A⁴ is C—H; G¹ is oxygen; L is a single bond or methyl; R¹ ishydrogen; R² is hydrogen; R³ is chlorodifluoromethyl or trifluoromethyl;R⁴ is phenyl or phenyl substituted by one to three R⁶; Y² is S, SO, orSO₂, and Y¹ and Y³ are independently of another CR⁷R⁸; R⁵ is bromo,chloro, fluoro, cyano, nitro, methyl, ethyl, trifluoromethyl, methoxy,difluoromethoxy, trifluoromethoxy, or methoxycarbonyl-; each R⁶ isindependently chloro, fluoro, cyano, nitro, methyl, ethyl,trifluoromethyl, methoxy, or trifluoromethoxy; each R⁷ and R⁸ isindependently hydrogen or methyl.
 20. A compound according to claim 1wherein A¹ is C—R⁵; A² is C—H; A³ is C—H; and A⁴ is C—H; G¹ is oxygen; Lis a single bond; R¹ is hydrogen; R² is hydrogen; R³ is trifluoromethyl;R⁴ is phenyl substituted by one to three R⁶; Y² is S, SO, or SO₂, and Y¹and Y³ are independently of another CR⁷R⁸; R⁵ is chloro, fluoro ormethyl; each R⁶ is independently bromo, chloro or fluoro; each R⁷ and R⁸is independently hydrogen.
 21. A compound of formula Ia

wherein G¹ is oxygen, R¹ is hydrogen, R² is hydrogen, R⁵ is methyl, Y¹is CH₂, Y² is S, SO or SO₂, and Y³ is CH₂.